{ "site": "pepteyes.com", "disclaimer": "Educational information only. Not medical advice. Many listed compounds are not approved for human use.", "updated": "2026-08-01", "count": 73, "categories": [ { "id": "metabolic", "name": "Metabolic & Weight", "blurb": "Incretin and amylin analogs that alter appetite, glucose handling and body weight.", "icon": "metabolic" }, { "id": "growth", "name": "Growth Hormone Axis", "blurb": "GHRH analogs and ghrelin-receptor secretagogues that raise endogenous GH and IGF-1.", "icon": "growth" }, { "id": "healing", "name": "Healing & Tissue Repair", "blurb": "Compounds promoted for tendon, muscle, gut and wound repair — the widest evidence gaps on this site.", "icon": "healing" }, { "id": "immune", "name": "Immune & Anti-inflammatory", "blurb": "Thymic, antimicrobial and cytokine-modulating peptides.", "icon": "immune" }, { "id": "cognitive", "name": "Cognitive & Neurological", "blurb": "Neurotrophic and neuroprotective peptides, several approved only outside the West.", "icon": "cognitive" }, { "id": "longevity", "name": "Longevity & Mitochondrial", "blurb": "Telomere, senolytic and mitochondrial-derived peptides marketed for aging.", "icon": "longevity" }, { "id": "sexual", "name": "Sexual Health & Melanocortin", "blurb": "Melanocortin receptor agonists affecting desire, arousal and pigmentation.", "icon": "sexual" }, { "id": "hormonal", "name": "Hormonal & Reproductive", "blurb": "Peptides acting on the hypothalamic-pituitary-gonadal axis.", "icon": "hormonal" }, { "id": "gut", "name": "Gut & Gastrointestinal", "blurb": "Peptides acting on the gut lumen and mucosa — several approved, several barely absorbed by design.", "icon": "gut" }, { "id": "antimicrobial", "name": "Antimicrobial & Antibiotic", "blurb": "Peptide antibiotics in frontline hospital use, plus the host-defence peptides marketed as supplements.", "icon": "antimicrobial" }, { "id": "cardiac", "name": "Cardiac & Vascular", "blurb": "Natriuretic and vasopressin-family peptides — and a lesson in why surrogate endpoints mislead.", "icon": "cardiac" }, { "id": "ophthalmic", "name": "Ophthalmic", "blurb": "Peptides approved for the eye, where local delivery separates efficacy from systemic toxicity.", "icon": "ophthalmic" }, { "id": "cosmetic", "name": "Skin & Cosmetic", "blurb": "Topical peptides with human data for wrinkles, collagen and skin repair.", "icon": "cosmetic" }, { "id": "other", "name": "Bone, Muscle & Other", "blurb": "Bone-anabolic, myostatin-related, sleep and miscellaneous peptides.", "icon": "other" } ], "statusMeta": { "approved": { "label": "FDA Approved", "short": "Approved", "tone": "good", "desc": "Approved by the FDA for at least one indication." }, "limited": { "label": "Limited Approval", "short": "Limited", "tone": "warn", "desc": "Approved outside the US, formerly approved, or available only via compounding." }, "trials": { "label": "In Clinical Trials", "short": "In trials", "tone": "info", "desc": "Under formal investigation in registered human trials. Not approved." }, "research": { "label": "Research Use Only", "short": "Research only", "tone": "bad", "desc": "No approval anywhere for human use. Sold under research-use labelling." }, "cosmetic": { "label": "Cosmetic Ingredient", "short": "Cosmetic", "tone": "info", "desc": "Lawful topical cosmetic ingredient; not a therapeutic drug." }, "nonpeptide": { "label": "Not a Peptide", "short": "Not a peptide", "tone": "warn", "desc": "Included because it is marketed alongside peptides, but is a different class of molecule." } }, "evidenceMeta": { "1": { "label": "Minimal", "desc": "Animal or laboratory data only. No human efficacy evidence." }, "2": { "label": "Limited", "desc": "Preclinical work plus scattered human reports, uncontrolled use, or negative trials." }, "3": { "label": "Moderate", "desc": "Small or early-phase human trials, or good controlled topical human data." }, "4": { "label": "Strong", "desc": "Consistent human randomized trials, or approval outside the United States." }, "5": { "label": "Very strong", "desc": "Multiple phase 3 randomized trials plus regulatory approval in a major market." } }, "peptides": [ { "slug": "adipotide", "name": "Adipotide", "aka": [ "FTPP", "prohibitin-targeting peptide" ], "category": "other", "chemClass": "Peptidomimetic targeting prohibitin on adipose vasculature, fused to a pro-apoptotic domain", "route": "Subcutaneous (research)", "halfLife": "Short", "status": "research", "statusNote": "Development halted after primate studies showed dose-dependent kidney toxicity. Not approved.", "evidence": 1, "summary": "Designed to kill the blood supply feeding fat tissue. It worked in monkeys — and damaged their kidneys. Development stopped, and it is included here because it continues to be sold online to people unaware of why it was abandoned.", "mechanism": "A homing peptide targeting prohibitin, expressed on the endothelium of white adipose tissue vasculature, coupled to a pro-apoptotic peptide domain. Binding triggers apoptosis in the adipose blood supply, causing fat tissue to regress from ischemia.", "studied": "Obese rhesus monkey studies showing rapid weight loss alongside renal toxicity; rodent studies. Human trials were not pursued.", "benefits": [ { "t": "Rapid fat loss in primates", "d": "Obese monkeys lost roughly 11% of body weight in four weeks with improved insulin sensitivity.", "s": "preliminary" }, { "t": "Novel targeting mechanism", "d": "Vascular targeting of adipose tissue is scientifically interesting and mechanistically distinct from appetite-based approaches.", "s": "preliminary" } ], "risks": [ { "t": "Dose-dependent nephrotoxicity", "d": "Kidney damage in primate studies was the reason development stopped. This is not a theoretical concern.", "s": "high" }, { "t": "No human trials ever conducted", "d": "It never reached humans in a controlled setting, by decision rather than accident.", "s": "high" }, { "t": "Non-selective apoptosis", "d": "Prohibitin is expressed elsewhere; off-target vascular apoptosis is a design-level risk.", "s": "high" }, { "t": "Still sold online", "d": "Marketed to consumers who are generally unaware it was abandoned for toxicity.", "s": "high" } ], "avoid": [ "All human use" ], "monitoring": [ "Not applicable" ], "legal": "Not approved. Development discontinued.", "evidenceNotes": [ "Abandoned for documented organ toxicity in primates — the clearest possible negative signal short of a human trial." ], "tags": [ "fat loss", "discontinued", "nephrotoxicity", "high risk" ] }, { "slug": "afamelanotide", "name": "Afamelanotide", "aka": [ "Melanotan I", "Scenesse", "NDP-MSH" ], "category": "sexual", "chemClass": "Selective MC1R agonist — alpha-MSH analog", "route": "Subcutaneous implant (controlled release over ~2 months)", "halfLife": "Implant releases over approximately 2 months", "status": "approved", "statusNote": "FDA-approved (2019) and EMA-approved to increase pain-free light exposure in adults with erythropoietic protoporphyria", "evidence": 5, "summary": "The properly developed sibling of Melanotan II — selective for MC1R, delivered as a controlled-release implant by a physician, and approved for a rare photosensitivity disorder. It shows what the melanocortin pigmentation mechanism looks like when taken through real drug development.", "mechanism": "Selective MC1R agonism increases eumelanin production in the skin, providing photoprotection. In erythropoietic protoporphyria, this reduces the excruciating phototoxic pain that follows even brief light exposure.", "studied": "Randomized controlled trials in erythropoietic protoporphyria in the US and Europe; long-term post-authorisation safety registries.", "benefits": [ { "t": "Increased pain-free light exposure in EPP", "d": "Randomized trials showed significant increases in time spent in direct sunlight without pain — transformative for a condition that otherwise confines patients indoors.", "s": "strong" }, { "t": "Improved quality of life", "d": "Validated quality-of-life measures improved substantially in trials and registries.", "s": "strong" }, { "t": "Receptor selectivity", "d": "MC1R selectivity avoids most of the MC4R and MC5R effects that make Melanotan II unpredictable.", "s": "strong" }, { "t": "Controlled physician-administered delivery", "d": "The implant removes dosing guesswork and self-injection risk entirely.", "s": "strong" } ], "risks": [ { "t": "Generalised skin darkening", "d": "Expected and on-target, but cosmetically significant and unavoidable.", "s": "low" }, { "t": "Implant site reactions", "d": "Local reactions at the subcutaneous implant site are the most common adverse event.", "s": "low" }, { "t": "Melanocytic lesion monitoring required", "d": "Twice-yearly full-body skin examination is required by the label; it does not remove the need for sun protection.", "s": "moderate" }, { "t": "Nausea, headache, fatigue", "d": "Reported in trials, generally mild to moderate.", "s": "low" }, { "t": "Very restricted indication and access", "d": "Only for erythropoietic protoporphyria, administered in certified centres. It is not available or appropriate as a tanning product.", "s": "moderate" } ], "avoid": [ "Anyone without erythropoietic protoporphyria", "Hepatic impairment", "Pregnancy" ], "monitoring": [ "Full-body skin examination twice yearly", "Liver function", "Implant site assessment" ], "legal": "Approved prescription implant, administered by certified healthcare professionals only.", "evidenceNotes": [ "Randomized trials plus ongoing post-authorisation safety registries." ], "tags": [ "photoprotection", "rare disease", "melanocortin", "approved", "EPP" ], "confusedWith": [ { "slug": "melanotan-ii", "why": "Afamelanotide is Melanotan I: selective, approved, physician-implanted, for a rare disease. Melanotan II is non-selective, unapproved, self-injected, and carries worldwide regulator warnings." } ] }, { "slug": "aod-9604", "name": "AOD-9604", "aka": [ "hGH fragment 176-191" ], "category": "metabolic", "chemClass": "C-terminal fragment of human growth hormone (residues 176–191)", "route": "Subcutaneous or oral (research)", "halfLife": "Short; poorly characterised in humans", "status": "research", "statusNote": "Failed clinical development for obesity. Not approved. FDA has rejected it as a dietary supplement ingredient.", "evidence": 2, "summary": "Marketed as \"the fat-loss fragment of growth hormone without the growth hormone side effects\". The marketing outlived the science: the clinical trials that tested exactly that claim did not show meaningful weight loss.", "mechanism": "Proposed to stimulate lipolysis and inhibit lipogenesis via beta-3 adrenergic signalling in adipose tissue, without binding the GH receptor and therefore without raising IGF-1. The mechanism is plausible in rodent adipocytes; translation to humans was not demonstrated.", "studied": "Phase 2 obesity trials conducted in the 2000s; later small studies in osteoarthritis with intra-articular delivery.", "benefits": [ { "t": "Does not raise IGF-1", "d": "Human studies consistently confirm no meaningful effect on IGF-1 or blood glucose — its safety claim, at least, held up.", "s": "moderate" }, { "t": "Good short-term tolerability", "d": "Trials reported an adverse-event profile close to placebo.", "s": "moderate" }, { "t": "Preclinical lipolytic activity", "d": "Rodent and in-vitro adipocyte data show fat mobilisation.", "s": "preliminary" } ], "risks": [ { "t": "No demonstrated efficacy", "d": "The pivotal obesity trials did not separate from placebo on weight loss. This is the central fact about AOD-9604.", "s": "high" }, { "t": "Unapproved and unregulated", "d": "Sold as a \"research chemical\" or in illegal supplements; the FDA has issued warning letters over it.", "s": "high" }, { "t": "Unknown long-term safety", "d": "No chronic human exposure data.", "s": "moderate" }, { "t": "Prohibited in sport", "d": "Listed by WADA.", "s": "low" } ], "avoid": [ "Anyone seeking evidence-based weight loss — approved options vastly outperform it" ], "monitoring": [ "Not applicable" ], "legal": "Not approved. FDA has determined it is not lawful as a dietary ingredient.", "evidenceNotes": [ "Negative phase 2 results are the highest-quality evidence available." ], "tags": [ "fat loss", "failed trials", "growth hormone fragment" ], "confusedWith": [ { "slug": "somatropin", "why": "AOD-9604 is a fragment of growth hormone marketed as giving fat loss without GH side effects. It also failed to produce weight loss in its phase 2 trials, which somatropin does not." } ] }, { "slug": "ara-290", "name": "ARA-290 (Cibinetide)", "aka": [ "Cibinetide", "pHBSP" ], "category": "healing", "chemClass": "11-amino-acid peptide derived from the helix B region of erythropoietin", "route": "Subcutaneous (investigational)", "halfLife": "~2 minutes (tissue effects far outlast plasma levels)", "status": "trials", "statusNote": "Investigational. Phase 2 trials in sarcoidosis-associated small fibre neuropathy. Not approved.", "evidence": 3, "summary": "An elegant piece of drug design: it takes the tissue-protective part of erythropoietin and discards the part that makes red blood cells. That separation removes the thrombotic risk that makes EPO dangerous, leaving only the repair signalling.", "mechanism": "Binds the innate repair receptor — a heterocomplex of the EPO receptor beta-common chain — rather than the classical homodimeric EPO receptor. This triggers anti-inflammatory and tissue-protective signalling without stimulating erythropoiesis.", "studied": "Phase 2 randomized trials in sarcoidosis-associated small fibre neuropathy and in type 2 diabetes with neuropathic pain; preclinical work across neuropathy, wound and ischemia models.", "benefits": [ { "t": "Improved neuropathic symptoms in phase 2", "d": "Randomized trials in sarcoidosis-related small fibre neuropathy showed improvement in pain and autonomic symptom scores versus placebo.", "s": "moderate" }, { "t": "Increased corneal nerve fibre density", "d": "An objective imaging endpoint suggesting genuine nerve regeneration, not just symptom relief.", "s": "moderate" }, { "t": "No erythropoietic effect", "d": "Does not raise haematocrit, avoiding the thrombosis and hypertension risks that limit EPO.", "s": "strong" }, { "t": "Good tolerability in trials", "d": "Adverse event rates comparable to placebo in phase 2.", "s": "moderate" } ], "risks": [ { "t": "Not approved; development slow", "d": "Despite encouraging phase 2 data across several years, it has not reached approval.", "s": "high" }, { "t": "Small trials", "d": "Phase 2 populations were modest in size, in a condition with substantial placebo response.", "s": "moderate" }, { "t": "Extremely short plasma half-life", "d": "Requires assuming that brief receptor engagement produces lasting tissue effects — plausible but not fully established.", "s": "moderate" }, { "t": "Injection-site reactions", "d": "The most commonly reported adverse effect.", "s": "low" }, { "t": "Grey-market availability", "d": "Sold as a research peptide well outside the neuropathy contexts studied.", "s": "high" } ], "avoid": [ "Use outside clinical trials", "Pregnancy" ], "monitoring": [ "Not applicable outside trials" ], "legal": "Investigational; not approved in any market.", "evidenceNotes": [ "Genuine randomized phase 2 data with an objective corneal nerve imaging endpoint — better than most compounds in this category." ], "tags": [ "neuropathy", "erythropoietin", "tissue repair", "investigational" ] }, { "slug": "argireline", "name": "Argireline (Acetyl Hexapeptide-8)", "aka": [ "Acetyl hexapeptide-3", "AH8" ], "category": "cosmetic", "chemClass": "Synthetic hexapeptide modelled on the N-terminal end of SNAP-25", "route": "Topical", "halfLife": "Not applicable — topical, non-systemic", "status": "cosmetic", "statusNote": "Widely used cosmetic ingredient with published human topical studies. Not a drug; makes cosmetic rather than therapeutic claims.", "evidence": 3, "summary": "Marketed as \"topical Botox\", which overstates it considerably. It does work by a related mechanism, and controlled studies do show measurable wrinkle-depth reduction — just far smaller than injectable neuromodulators.", "mechanism": "Mimics the N-terminal of SNAP-25 and competes for a position in the SNARE complex required for vesicular acetylcholine release at the neuromuscular junction, modestly reducing muscle contraction. Botulinum toxin cleaves SNAP-25 outright, which is why the effect sizes differ so much.", "studied": "Several controlled topical studies measuring wrinkle depth by profilometry and image analysis over 4–12 weeks.", "benefits": [ { "t": "Measurable wrinkle-depth reduction", "d": "Controlled studies report reductions on the order of 10–30% in expression-line depth over 4–8 weeks — modest but real and objectively measured.", "s": "moderate" }, { "t": "Excellent safety profile", "d": "Topical, non-systemic, and very well tolerated across studies.", "s": "strong" }, { "t": "No injections or downtime", "d": "The practical appeal: no needles, no procedure, no recovery.", "s": "strong" }, { "t": "Compatible with most routines", "d": "Water-soluble and stable in typical cosmetic formulations.", "s": "moderate" } ], "risks": [ { "t": "Far weaker than injectable neuromodulators", "d": "Comparing it to botulinum toxin sets expectations it cannot meet.", "s": "low" }, { "t": "Limited skin penetration", "d": "A hexapeptide crossing the stratum corneum in meaningful quantity is a genuine formulation challenge; delivery system matters enormously.", "s": "moderate" }, { "t": "Effects reverse on stopping", "d": "Continuous use is required to maintain any benefit.", "s": "low" }, { "t": "Industry-funded evidence base", "d": "Much of the supporting research comes from ingredient manufacturers.", "s": "moderate" }, { "t": "Mild irritation in sensitive skin", "d": "Uncommon and generally minor.", "s": "low" } ], "avoid": [ "Known peptide or formulation ingredient allergy", "Broken or irritated skin" ], "monitoring": [ "None required" ], "legal": "Lawful cosmetic ingredient in the US, EU and most markets.", "evidenceNotes": [ "Objective outcome measures, small effect sizes, significant industry funding." ], "tags": [ "skin", "wrinkles", "topical", "cosmetic", "SNAP-25" ] }, { "slug": "bpc-157", "name": "BPC-157", "aka": [ "Body Protection Compound 157", "Pentadecapeptide BPC 157" ], "category": "healing", "chemClass": "Synthetic pentadecapeptide derived from a sequence in human gastric juice protein BPC", "route": "Oral or subcutaneous (research)", "halfLife": "Not established in humans", "status": "research", "statusNote": "Not approved. FDA placed BPC-157 in Category 2 of its bulk-substance review in 2023, barring it from lawful compounding. WADA-prohibited since 2022.", "evidence": 1, "summary": "The single most popular peptide in the wellness market, and the widest gap on this site between reputation and evidence. Hundreds of rodent studies show impressive healing effects. Published randomized human trials showing the same: none.", "mechanism": "Proposed to upregulate VEGFR2 signalling and angiogenesis, modulate nitric oxide pathways, increase fibroblast migration and tendon-derived cell outgrowth, and interact with the gut-brain axis. Mechanistic work is almost entirely rodent and in-vitro.", "studied": "Extensive rodent models of tendon, ligament, muscle, bone, gut and nerve injury, largely from a small number of affiliated research groups. Early human safety work exists for an oral formulation in inflammatory bowel disease; efficacy results were never published in the peer-reviewed literature.", "benefits": [ { "t": "Consistent tendon and ligament healing in rodents", "d": "Multiple animal models show accelerated tendon-to-bone healing and improved biomechanical strength. The animal literature is genuinely large and internally consistent.", "s": "preliminary" }, { "t": "Gut protection in animal models", "d": "Protects against NSAID-induced and other experimental gut injury in rodents, which is where the compound originated.", "s": "preliminary" }, { "t": "Angiogenic activity", "d": "Promotes new blood-vessel formation in preclinical models — the likely common mechanism behind the varied healing effects.", "s": "preliminary" }, { "t": "Low acute toxicity in animals", "d": "Rodent toxicology has not identified a clear toxic dose, though this says little about chronic human exposure.", "s": "preliminary" } ], "risks": [ { "t": "No published randomized human trials", "d": "Every efficacy claim made for BPC-157 in humans is extrapolated from rodents or drawn from anecdote. This is the central fact about it.", "s": "high" }, { "t": "Angiogenesis cuts both ways", "d": "The same new-blood-vessel formation that helps a tendon heal is a mechanism tumours depend on. There is no data on use in people with occult or prior malignancy.", "s": "high" }, { "t": "Banned from compounding by FDA", "d": "FDA concluded there was insufficient safety information to permit compounding — a formal regulatory judgement, not an oversight.", "s": "high" }, { "t": "Product quality is frequently poor", "d": "Independent testing of grey-market peptide vials has repeatedly found incorrect content, degradation products, and bacterial contamination.", "s": "high" }, { "t": "Unknown long-term effects", "d": "No chronic exposure data at all. Users are the study population.", "s": "high" }, { "t": "Prohibited in sport", "d": "Added to the WADA prohibited list in 2022; athletes have been sanctioned.", "s": "moderate" } ], "avoid": [ "Anyone with a cancer history or undiagnosed mass", "Pregnancy and breastfeeding", "Tested athletes", "Anyone who cannot verify product identity and sterility" ], "monitoring": [ "No validated monitoring exists; discuss any use with your physician" ], "legal": "Not an approved drug. Not a lawful dietary supplement. Not eligible for pharmacy compounding in the US. Sold under \"research use only\" labelling that does not confer legality for human use.", "evidenceNotes": [ "Rodent evidence base is unusually large for a research peptide — but preclinical promise routinely fails to replicate in humans.", "The absence of human trials after two decades of interest is itself informative." ], "tags": [ "tendon", "gut health", "injury recovery", "research chemical", "popular" ], "confusedWith": [ { "slug": "pentadeca-arginate", "why": "PDA is the same pentadecapeptide as an arginate salt, marketed as a compliant alternative after FDA barred BPC-157 from compounding. Renaming a substance does not make it approved, and PDA has no independent studies of its own." }, { "slug": "tb-500", "why": "Routinely sold and used together for injury recovery. Neither has published randomized human trials for musculoskeletal healing, and both are WADA-prohibited." } ] }, { "slug": "cagrilintide", "name": "Cagrilintide", "aka": [ "CagriSema (with semaglutide)" ], "category": "metabolic", "chemClass": "Long-acting amylin analog", "route": "Subcutaneous, once weekly (investigational)", "halfLife": "~7 days", "status": "trials", "statusNote": "Phase 3 (REDEFINE program) as a fixed combination with semaglutide. Not approved.", "evidence": 3, "summary": "Amylin is the pancreatic hormone co-secreted with insulin that signals meal termination through a pathway separate from GLP-1. Combining the two mechanisms is the leading strategy for pushing weight loss past the incretin ceiling.", "mechanism": "Activates amylin and calcitonin receptor complexes in the area postrema, slowing gastric emptying and producing satiation. Because the receptor population differs from GLP-1, effects are additive rather than redundant.", "studied": "REDEFINE phase 3 program in obesity; earlier phase 2 combination trials.", "benefits": [ { "t": "Additive weight loss with semaglutide", "d": "Combination phase 3 data reported mean weight reduction above 20%, exceeding either component alone.", "s": "moderate" }, { "t": "Complementary satiety mechanism", "d": "Amylin signalling may preserve efficacy where GLP-1 response plateaus.", "s": "preliminary" }, { "t": "Possible lean-mass sparing", "d": "Amylin analogs have been hypothesised to shift the fat-to-lean loss ratio favourably; this remains under investigation.", "s": "preliminary" } ], "risks": [ { "t": "Not approved", "d": "No regulatory authorisation anywhere; safety profile is still being characterised.", "s": "high" }, { "t": "GI adverse effects", "d": "Nausea and vomiting remain the dominant tolerability limit in combination.", "s": "moderate" }, { "t": "Variable individual response", "d": "Phase 3 results showed a wide response distribution and notable proportions of participants not reaching target doses.", "s": "moderate" }, { "t": "Grey-market availability", "d": "Sold illicitly as a \"research peptide\" with no quality control.", "s": "high" } ], "avoid": [ "Use outside clinical trials" ], "monitoring": [ "Not applicable outside trials" ], "legal": "Investigational. Not lawfully available for human use.", "evidenceNotes": [ "Phase 3 topline data reported; full peer-reviewed publication and regulatory review pending." ], "tags": [ "weight loss", "amylin", "investigational", "combination" ] }, { "slug": "cenegermin", "name": "Cenegermin", "aka": [ "Oxervate", "recombinant human nerve growth factor" ], "category": "ophthalmic", "chemClass": "Recombinant human nerve growth factor — a 118-amino-acid protein", "route": "Ophthalmic drops, six times daily for 8 weeks", "halfLife": "Local ocular action; negligible systemic exposure", "status": "approved", "statusNote": "FDA-approved (2018) and EMA-approved for neurotrophic keratitis — the first approved treatment for that condition.", "evidence": 5, "summary": "The first drug ever approved for neurotrophic keratitis, a degenerative disease in which the cornea loses its nerve supply and stops healing. It is a growth factor delivered as an eye drop, and it heals corneal ulcers that previously required surgery.", "mechanism": "Recombinant human NGF binds TrkA and p75 receptors on corneal epithelial cells, sensory nerve endings and limbal stem cells, restoring the trophic signalling that maintains corneal integrity. Because the cornea and its nerves are damaged in the same disease process, supplying NGF supports both.", "studied": "REPARO and a second phase 3 randomized vehicle-controlled trial in moderate to severe neurotrophic keratitis, with long-term follow-up.", "benefits": [ { "t": "Heals persistent corneal defects", "d": "Roughly 70% of treated patients achieved complete corneal healing at 8 weeks versus far fewer on vehicle, in randomized trials.", "s": "strong" }, { "t": "First approved therapy for the condition", "d": "Previously management was limited to lubricants, bandage lenses and surgical options such as tarsorrhaphy.", "s": "strong" }, { "t": "Durable healing", "d": "Follow-up showed most healed patients remained healed after treatment ended.", "s": "moderate" }, { "t": "Restores corneal sensitivity in some patients", "d": "Consistent with genuine nerve regeneration rather than surface healing alone.", "s": "moderate" } ], "risks": [ { "t": "Eye pain during treatment", "d": "The most common adverse effect, and mechanistically expected — restored corneal sensation in a previously anaesthetic eye is uncomfortable.", "s": "moderate" }, { "t": "Demanding regimen", "d": "Six drops daily for eight weeks, with strict cold-chain handling and a specific administration schedule. Adherence is a genuine problem.", "s": "moderate" }, { "t": "Ocular hyperaemia and inflammation", "d": "Common, generally resolving after the treatment course.", "s": "low" }, { "t": "Very high cost", "d": "Among the most expensive ophthalmic treatment courses available.", "s": "moderate" }, { "t": "Narrow indication", "d": "Approved only for neurotrophic keratitis; there is no evidence for use in ordinary dry eye.", "s": "moderate" } ], "avoid": [ "Use for conditions other than neurotrophic keratitis", "Contact lens wear during treatment", "Known hypersensitivity to the formulation" ], "monitoring": [ "Corneal healing by slit-lamp examination", "Corneal sensitivity testing", "Symptom assessment during the 8-week course" ], "legal": "Prescription ophthalmic drug, supplied through specialty distribution with cold-chain requirements.", "evidenceNotes": [ "Two randomized vehicle-controlled phase 3 trials with an objective imaging-confirmed endpoint." ], "interactions": [ "No significant systemic interactions", "Other eye drops — separate instillation by at least 15 minutes" ], "tags": [ "cornea", "nerve growth factor", "rare disease", "approved", "eye" ] }, { "slug": "cerebrolysin", "name": "Cerebrolysin", "aka": [ "FPF-1070" ], "category": "cognitive", "chemClass": "Porcine brain-derived peptide preparation — a mixture, not a single molecule", "route": "Intravenous or intramuscular", "halfLife": "Not applicable — heterogeneous mixture", "status": "limited", "statusNote": "Approved in around 40 countries for stroke, dementia and traumatic brain injury. Not approved in the US, UK or most of Western Europe.", "evidence": 3, "summary": "Widely used across Eastern Europe and Asia, and one of the few peptide products with Cochrane systematic reviews. Those reviews are not favourable, which makes this a useful case study in how volume of use and quality of evidence can diverge.", "mechanism": "Enzymatically processed porcine brain protein yielding low-molecular-weight peptides and amino acids with claimed neurotrophic activity mimicking endogenous factors such as BDNF and GDNF. The exact active constituents are not fully defined.", "studied": "Numerous randomized trials in acute ischemic stroke, vascular dementia, Alzheimer disease and traumatic brain injury; multiple Cochrane systematic reviews.", "benefits": [ { "t": "Some cognitive benefit signals in vascular dementia", "d": "Meta-analyses of dementia trials report modest cognitive score improvements, though effect sizes are small and heterogeneity is high.", "s": "preliminary" }, { "t": "Large accumulated clinical experience", "d": "Decades of use across many countries with an extensive, if uneven, literature.", "s": "moderate" }, { "t": "Neurotrophic activity in preclinical models", "d": "Animal work supports neuroprotection and neurogenesis effects.", "s": "preliminary" } ], "risks": [ { "t": "Cochrane review found no benefit in acute stroke", "d": "The systematic review concluded there was no evidence of benefit on death or dependence — the outcomes that matter most.", "s": "high" }, { "t": "Possible increase in serious adverse events", "d": "The same review raised a signal for non-fatal serious adverse events, though confidence intervals were wide.", "s": "high" }, { "t": "Porcine biological source", "d": "Carries theoretical transmissible agent concerns and is unacceptable to some patients on religious grounds.", "s": "moderate" }, { "t": "Undefined composition", "d": "A mixture whose active components are not fully characterised, complicating batch consistency and mechanism attribution.", "s": "moderate" }, { "t": "Anaphylaxis and hypersensitivity", "d": "Reported with a foreign-protein-derived product.", "s": "moderate" }, { "t": "Trial quality and publication bias concerns", "d": "Much of the positive literature comes from a limited set of investigators and sponsors.", "s": "high" } ], "avoid": [ "Epilepsy (relative — seizure reports exist)", "Severe renal impairment", "Pregnancy", "Known protein hypersensitivity" ], "monitoring": [ "Renal function", "Allergic reaction observation during infusion", "Cognitive assessment scales" ], "legal": "Approved in many countries; unapproved and not lawfully marketed in the US.", "evidenceNotes": [ "Unusual for a peptide product: enough trials to be systematically reviewed. The reviews are the key evidence." ], "tags": [ "stroke", "dementia", "neurotrophic", "porcine", "Cochrane-reviewed" ] }, { "slug": "ciclosporin", "name": "Ciclosporin (Cyclosporine A)", "aka": [ "Restasis", "Cequa", "Neoral", "Sandimmune", "cyclosporin A" ], "category": "ophthalmic", "chemClass": "Cyclic undecapeptide of fungal origin, containing several non-standard amino acids", "route": "Ophthalmic emulsion; also oral and intravenous for systemic use", "halfLife": "~8–27 hours systemically; ophthalmic use gives negligible systemic exposure", "status": "approved", "statusNote": "FDA-approved as an ophthalmic emulsion for keratoconjunctivitis sicca, and systemically for transplant rejection prophylaxis and several autoimmune conditions.", "evidence": 5, "summary": "Genuinely a peptide — a cyclic eleven-residue peptide made by a soil fungus — and arguably the most consequential one in medicine. It made organ transplantation routine. Its ophthalmic form is the reason chronic dry eye became a treatable inflammatory disease rather than something you managed with drops.", "mechanism": "Binds cyclophilin; the complex inhibits calcineurin, blocking dephosphorylation of NFAT and preventing transcription of IL-2 and other cytokines required for T-cell activation. On the ocular surface this interrupts the self-sustaining inflammatory cycle that damages lacrimal tissue.", "studied": "Large randomized trials in transplantation, psoriasis and rheumatoid arthritis; multiple randomized ophthalmic trials in dry eye disease.", "benefits": [ { "t": "Treats the cause of dry eye, not just symptoms", "d": "Randomized trials showed increased tear production by Schirmer testing — restored function rather than lubrication alone.", "s": "strong" }, { "t": "Made modern transplantation possible", "d": "Systemic ciclosporin transformed graft survival rates and is among the most consequential drugs of the twentieth century.", "s": "strong" }, { "t": "Negligible systemic exposure ophthalmically", "d": "Blood levels after topical ocular use are generally undetectable, so systemic toxicities do not apply.", "s": "strong" }, { "t": "Steroid-sparing on the ocular surface", "d": "Avoids the cataract and intraocular pressure risks of long-term topical steroids.", "s": "strong" }, { "t": "Effective in several autoimmune diseases", "d": "Systemic use has randomized evidence in severe psoriasis, rheumatoid arthritis and nephrotic syndrome.", "s": "strong" } ], "risks": [ { "t": "Systemic use is nephrotoxic", "d": "Dose-related and often progressive renal impairment is the principal limitation of oral ciclosporin, requiring level monitoring throughout.", "s": "high" }, { "t": "Systemic use raises malignancy and infection risk", "d": "Sustained T-cell suppression increases lymphoma, skin cancer and opportunistic infection risk. None of this applies to eye drops.", "s": "high" }, { "t": "Ocular burning on instillation", "d": "The most common complaint with the emulsion and a frequent reason for stopping.", "s": "moderate" }, { "t": "Slow onset ophthalmically", "d": "Benefit typically takes 3–6 months, and many patients abandon treatment before it appears.", "s": "moderate" }, { "t": "Systemic hypertension and gum hyperplasia", "d": "Common with oral therapy; irrelevant to ophthalmic use.", "s": "moderate" }, { "t": "Extensive systemic drug interactions", "d": "A CYP3A4 substrate with a long and clinically important interaction list.", "s": "high" } ], "avoid": [ "Ocular infection — do not use the emulsion during active infection", "Systemic use: uncontrolled hypertension, significant renal impairment, active malignancy", "Contact lenses should be removed before instillation and reinserted after 15 minutes" ], "monitoring": [ "Ophthalmic: symptom and Schirmer response at 3–6 months", "Systemic: trough levels, serum creatinine, blood pressure, potassium, lipids", "Systemic: skin surveillance for malignancy" ], "legal": "Prescription drug in both ophthalmic and systemic forms.", "evidenceNotes": [ "One of the most thoroughly studied drugs in medicine, across transplantation, rheumatology, dermatology and ophthalmology.", "Ophthalmic and systemic risk profiles are almost entirely separate — do not transfer one to the other." ], "interactions": [ "Systemic: CYP3A4 inhibitors (ketoconazole, macrolides, grapefruit) raise levels sharply", "Systemic: CYP3A4 inducers (rifampicin, phenytoin, St John's wort) cause graft-threatening drops", "Systemic: statins — increased rhabdomyolysis risk", "Systemic: NSAIDs and aminoglycosides — additive nephrotoxicity", "Ophthalmic: minimal, given negligible absorption" ], "tags": [ "dry eye", "transplant", "immunosuppressant", "cyclic peptide", "approved" ] }, { "slug": "cjc-1295", "name": "CJC-1295", "aka": [ "Modified GRF (1-29)", "CJC-1295 with DAC", "tesamorelin cousin" ], "category": "growth", "chemClass": "GHRH analog; the DAC version bears a maleimide linker that binds serum albumin", "route": "Subcutaneous (research)", "halfLife": "Non-DAC ~30 minutes; with DAC roughly 6–8 days", "status": "research", "statusNote": "Investigational; clinical development discontinued. Not approved. Widely sold grey-market.", "evidence": 2, "summary": "Two different compounds share this name, which is a persistent source of confusion. The DAC version lasts a week and produces a sustained GH elevation; the non-DAC version behaves like sermorelin. Neither completed development.", "mechanism": "GHRH receptor agonism. The Drug Affinity Complex covalently binds circulating albumin, extending half-life from minutes to days and converting pulsatile stimulation into a continuous \"bleed\" of GH — a pharmacology quite unlike natural secretion.", "studied": "Small phase 1 pharmacokinetic and safety studies in healthy adults; development halted.", "benefits": [ { "t": "Sustained GH and IGF-1 elevation", "d": "Phase 1 data showed multi-day increases in GH and IGF-1 after a single DAC dose — the pharmacology works as designed.", "s": "moderate" }, { "t": "Reduced injection frequency", "d": "The DAC version requires weekly rather than daily dosing.", "s": "moderate" }, { "t": "Synergy with ghrelin agonists", "d": "Combining a GHRH analog with a GHRP produces a larger GH pulse than either alone — well established in pituitary physiology.", "s": "moderate" } ], "risks": [ { "t": "Continuous GH exposure is non-physiological", "d": "Natural GH is pulsatile. Chronic flat elevation is the pattern seen in acromegaly, and its long-term consequences with this drug are untested.", "s": "high" }, { "t": "Development discontinued", "d": "The sponsor stopped work; no phase 2 or 3 efficacy or safety data exist.", "s": "high" }, { "t": "Insulin resistance and glucose elevation", "d": "Expected with sustained GH/IGF-1 elevation.", "s": "moderate" }, { "t": "Fluid retention, paraesthesia, carpal tunnel", "d": "GH-excess symptoms reported by users.", "s": "moderate" }, { "t": "Theoretical cancer promotion", "d": "IGF-1 is mitogenic; chronic elevation in people with occult neoplasia is a genuine unknown.", "s": "high" }, { "t": "Grey-market product quality", "d": "Sold as \"research use only\" with no pharmaceutical oversight, and frequently mislabelled as to DAC status.", "s": "high" }, { "t": "Banned in sport", "d": "Prohibited by WADA at all times.", "s": "low" } ], "avoid": [ "Active or prior malignancy", "Pregnancy", "Diabetes or insulin resistance", "Anyone in tested sport" ], "monitoring": [ "IGF-1", "Fasting glucose, HbA1c", "Blood pressure, oedema" ], "legal": "Not approved for human use in the US, EU or UK. Sale for human consumption is unlawful.", "evidenceNotes": [ "Human data limited to phase 1 pharmacokinetics.", "No efficacy trial for any clinical outcome has been completed." ], "tags": [ "growth hormone", "GHRH", "research chemical", "IGF-1" ], "interactions": [ "Insulin and oral hypoglycemics — GH elevation opposes insulin action, and requirements may increase", "Corticosteroids — blunt the GH response", "Thyroid hormone — GH axis changes can alter thyroid function testing" ], "confusedWith": [ { "slug": "sermorelin", "why": "CJC-1295 without DAC is functionally a sermorelin analog with a slightly longer half-life. CJC-1295 with DAC lasts about a week and produces continuous rather than pulsatile GH elevation — a fundamentally different exposure pattern. Vendors frequently do not specify which one they are selling." }, { "slug": "ipamorelin", "why": "Different mechanisms, routinely combined. CJC-1295 acts on the GHRH receptor; ipamorelin acts on the ghrelin receptor. Neither combination has been tested in a clinical trial." } ] }, { "slug": "colistin", "name": "Colistin (Polymyxin E)", "aka": [ "Colistimethate sodium", "Coly-Mycin M", "polymyxin E" ], "category": "antimicrobial", "chemClass": "Cyclic cationic polypeptide antibiotic with a fatty acyl tail", "route": "Intravenous, inhaled, or topical", "halfLife": "~2–3 hours (colistin base, after conversion from the prodrug)", "status": "approved", "statusNote": "FDA-approved. Abandoned in the 1970s for toxicity, then reintroduced as a last-resort agent against multidrug-resistant Gram-negative organisms.", "evidence": 4, "summary": "An antibiotic that was shelved for being too toxic and brought back because the alternative became no antibiotic at all. Its return is one of the clearest markers of how far Gram-negative resistance has progressed.", "mechanism": "The polycationic peptide binds lipid A in the Gram-negative outer membrane, displacing the divalent cations that stabilise lipopolysaccharide. The membrane becomes permeable and the cell dies. The same affinity for anionic membranes explains its renal and neurological toxicity.", "studied": "Extensive observational and registry data in carbapenem-resistant infection; randomized trials comparing colistin monotherapy with combination regimens.", "benefits": [ { "t": "Activity against carbapenem-resistant organisms", "d": "Retains activity against many multidrug-resistant Acinetobacter, Pseudomonas and Klebsiella isolates where nothing else works.", "s": "moderate" }, { "t": "Inhaled delivery for lung infection", "d": "Nebulised colistin achieves high airway concentrations with less systemic exposure, used particularly in cystic fibrosis.", "s": "moderate" }, { "t": "Slow resistance development historically", "d": "Decades of limited use kept resistance rates low, though the mobile mcr-1 resistance gene has changed that picture.", "s": "moderate" }, { "t": "A genuine last-resort option", "d": "Sometimes the only in-vitro active agent available.", "s": "strong" } ], "risks": [ { "t": "Nephrotoxicity in a large fraction of patients", "d": "Acute kidney injury occurs in a substantial proportion of treated patients and is the dominant limitation on its use.", "s": "high" }, { "t": "Neurotoxicity", "d": "Paraesthesia, dizziness, ataxia and, rarely, neuromuscular blockade causing respiratory arrest — particularly with concurrent neuromuscular blocking agents.", "s": "high" }, { "t": "Confusing dosing units", "d": "Colistimethate is dosed in international units in some countries and in colistin base activity milligrams in others. Unit confusion has caused serious dosing errors.", "s": "high" }, { "t": "Prodrug pharmacokinetics", "d": "Colistimethate must convert to active colistin, and conversion is slow and variable, complicating dosing in critical illness.", "s": "moderate" }, { "t": "Emerging plasmid-mediated resistance", "d": "The mcr-1 gene confers transferable colistin resistance and has spread internationally, largely driven by agricultural use.", "s": "high" }, { "t": "Weak evidence base by modern standards", "d": "Reintroduced without the trial program a new drug would require today.", "s": "moderate" } ], "avoid": [ "Concurrent neuromuscular blocking agents where avoidable", "Myasthenia gravis", "Pre-existing severe renal impairment (dose adjustment mandatory)", "Use when a less toxic active agent is available" ], "monitoring": [ "Serum creatinine daily in critical illness", "Neurological examination for paraesthesia and weakness", "Careful verification of dosing units", "Culture and susceptibility to confirm no better option exists" ], "legal": "Prescription antibiotic reserved for resistant infections.", "evidenceNotes": [ "Largely observational modern evidence — it re-entered practice out of necessity rather than through a trial program." ], "interactions": [ "Neuromuscular blocking agents — risk of prolonged paralysis and respiratory arrest", "Aminoglycosides and vancomycin — additive nephrotoxicity", "Loop diuretics — additive renal risk" ], "tags": [ "antibiotic", "last resort", "multidrug resistance", "polypeptide", "approved" ] }, { "slug": "daptomycin", "name": "Daptomycin", "aka": [ "Cubicin" ], "category": "antimicrobial", "chemClass": "Cyclic lipopeptide antibiotic — 13 amino acids with a decanoyl fatty acid tail", "route": "Intravenous, once daily", "halfLife": "~8–9 hours", "status": "approved", "statusNote": "FDA-approved for complicated skin and skin structure infections and for Staphylococcus aureus bacteraemia, including right-sided endocarditis.", "evidence": 5, "summary": "A reminder that peptides are not a fringe category — this is a frontline hospital antibiotic for MRSA bacteraemia, and it is a lipopeptide. It also carries one of the most instructive failures in antibiotic history: it does not work in the lungs, for a specific and knowable reason.", "mechanism": "The calcium-dependent lipid tail inserts into the Gram-positive bacterial membrane, oligomerises, and causes rapid membrane depolarisation and potassium efflux. The cell dies without lysis, which reduces the release of inflammatory cell-wall fragments compared with lytic antibiotics.", "studied": "Randomized non-inferiority trials in complicated skin infection and in S. aureus bacteraemia and endocarditis; a pneumonia trial that failed and defined a contraindication.", "benefits": [ { "t": "Effective against MRSA bacteraemia", "d": "Non-inferior to standard therapy in a randomized trial, and a mainstay option when vancomycin fails or cannot be used.", "s": "strong" }, { "t": "Rapid bactericidal activity", "d": "Concentration-dependent killing, generally faster than vancomycin in vitro.", "s": "strong" }, { "t": "Once-daily dosing", "d": "Practical for outpatient parenteral antibiotic therapy.", "s": "strong" }, { "t": "Non-lytic killing", "d": "Avoids the inflammatory burst associated with cell-wall-lysing agents.", "s": "moderate" } ], "risks": [ { "t": "Inactivated by pulmonary surfactant — useless in pneumonia", "d": "Its pneumonia trial failed because surfactant neutralises the drug in the alveolus. It must never be used for pneumonia, and this is a mechanism-level absolute.", "s": "high" }, { "t": "Rhabdomyolysis and myopathy", "d": "Creatine kinase must be monitored at least weekly; the drug is stopped if CK rises with muscle symptoms.", "s": "high" }, { "t": "Eosinophilic pneumonia", "d": "A distinct, serious hypersensitivity reaction that paradoxically affects the lungs, typically after 2 or more weeks of therapy.", "s": "high" }, { "t": "Peripheral neuropathy", "d": "Reported with prolonged therapy.", "s": "moderate" }, { "t": "Statin interaction", "d": "Concurrent statins compound muscle toxicity risk; many clinicians hold the statin during therapy.", "s": "moderate" }, { "t": "Resistance emergence on therapy", "d": "Non-susceptibility can develop during treatment of deep-seated infection, particularly with inadequate source control.", "s": "moderate" } ], "avoid": [ "Pneumonia — inactivated by surfactant", "Known daptomycin hypersensitivity", "Caution with concurrent statin therapy" ], "monitoring": [ "Creatine kinase at least weekly, more often with statins or renal impairment", "Renal function for dose adjustment", "New dyspnoea or fever after 2+ weeks — consider eosinophilic pneumonia", "Repeat blood cultures in bacteraemia" ], "legal": "Prescription antibiotic administered in hospital or outpatient parenteral settings.", "evidenceNotes": [ "Randomized non-inferiority trials plus two decades of hospital use.", "The negative pneumonia trial is as important as the positive ones." ], "interactions": [ "HMG-CoA reductase inhibitors (statins) — additive myopathy risk", "Tobramycin — increases daptomycin exposure", "Warfarin — monitor INR in the first days" ], "tags": [ "antibiotic", "MRSA", "lipopeptide", "approved", "hospital" ] }, { "slug": "davunetide", "name": "Davunetide", "aka": [ "NAP", "AL-108", "CP201" ], "category": "cognitive", "chemClass": "Eight-amino-acid fragment of activity-dependent neuroprotective protein (ADNP)", "route": "Intranasal or intravenous (investigational)", "halfLife": "Short; designed for CNS penetration", "status": "trials", "statusNote": "Failed a phase 3 trial in progressive supranuclear palsy in 2012. Later explored for ADNP syndrome. Not approved.", "evidence": 3, "summary": "One of the most instructive failures in neurology. Davunetide had a clean mechanism, encouraging phase 2 data, and a well-designed phase 3 trial in a tau disease — and it did nothing. Any peptide marketed for cognition should be measured against this outcome.", "mechanism": "Derived from ADNP, davunetide interacts with tubulin and microtubule end-binding proteins, stabilising the microtubule network. Because tau normally stabilises microtubules, the rationale was to substitute for tau function in diseases where tau is dysfunctional.", "studied": "Phase 2 in amnestic mild cognitive impairment and schizophrenia; a large randomized phase 3 trial in progressive supranuclear palsy; later work in ADNP syndrome.", "benefits": [ { "t": "Well-defined molecular mechanism", "d": "Microtubule stabilisation via end-binding proteins is demonstrable and specific.", "s": "moderate" }, { "t": "Encouraging phase 2 signals", "d": "Early trials suggested cognitive benefit in mild cognitive impairment and in schizophrenia-associated functional measures.", "s": "moderate" }, { "t": "Excellent safety profile", "d": "Well tolerated across trials including the large phase 3 — the failure was efficacy, not safety.", "s": "strong" }, { "t": "Rationale in ADNP syndrome", "d": "In a rare disorder caused by ADNP mutation, replacing the fragment has a clearer mechanistic case than in sporadic disease.", "s": "preliminary" } ], "risks": [ { "t": "Failed a well-designed phase 3", "d": "No benefit on any endpoint in progressive supranuclear palsy. This is the defining fact and it should temper enthusiasm for the whole neuroprotective peptide category.", "s": "high" }, { "t": "Phase 2 signals did not replicate", "d": "A textbook example of early cognitive signals disappearing under proper power and blinding.", "s": "high" }, { "t": "Not available", "d": "No approved product and no lawful supply.", "s": "moderate" }, { "t": "Nasal irritation", "d": "Reported with the intranasal formulation.", "s": "low" } ], "avoid": [ "Not applicable — no lawful supply exists" ], "monitoring": [ "Not applicable" ], "legal": "Investigational; development for the primary indication discontinued.", "evidenceNotes": [ "A properly powered negative phase 3 trial — high-quality evidence of absence of effect." ], "tags": [ "nootropic", "tau", "failed phase 3", "neuroprotection", "microtubule" ] }, { "slug": "desmopressin", "name": "Desmopressin", "aka": [ "DDAVP", "Nocdurna", "Stimate", "1-deamino-8-D-arginine vasopressin" ], "category": "cardiac", "chemClass": "Synthetic vasopressin analog — nonapeptide selective for the V2 receptor", "route": "Oral, intranasal, intravenous or subcutaneous", "halfLife": "~3 hours (biological effect considerably longer)", "status": "approved", "statusNote": "FDA-approved for central diabetes insipidus, primary nocturnal enuresis, nocturia, and for bleeding in mild haemophilia A and von Willebrand disease type 1.", "evidence": 5, "summary": "A textbook example of what targeted peptide engineering achieves. Two deliberate modifications to vasopressin removed the blood-pressure effect, kept the water-retention effect, and extended the duration — turning a pressor into a safe outpatient medicine with an unexpected second career in bleeding disorders.", "mechanism": "Selective V2 receptor agonism in the renal collecting duct inserts aquaporin-2 channels, concentrating urine. Deamination at position 1 and D-arginine substitution at position 8 remove V1-mediated vasoconstriction and slow degradation. V2 stimulation on endothelium also releases stored von Willebrand factor and factor VIII, which is the basis of the haemostatic indication.", "studied": "Decades of trials across diabetes insipidus, nocturia, enuresis, and haemostatic use in mild haemophilia A and von Willebrand disease.", "benefits": [ { "t": "Definitive therapy for central diabetes insipidus", "d": "Replaces the missing hormone directly, controlling polyuria and polydipsia — the clearest indication.", "s": "strong" }, { "t": "Releases von Willebrand factor and factor VIII", "d": "Raises levels several-fold within an hour, often avoiding blood product exposure for minor procedures in mild disease.", "s": "strong" }, { "t": "Reduces nocturia and nocturnal enuresis", "d": "Established efficacy with dedicated formulations and sex-specific dosing for nocturia.", "s": "strong" }, { "t": "No pressor effect", "d": "The V1 selectivity engineered out means it does not raise blood pressure the way vasopressin does.", "s": "strong" }, { "t": "Multiple routes available", "d": "Oral, sublingual, intranasal and injectable, allowing the route to match the indication.", "s": "strong" } ], "risks": [ { "t": "Hyponatremia — the central risk", "d": "Water retention without solute causes dilutional hyponatremia, which can progress to seizures and death. This has caused deaths in nocturia and enuresis treatment, and drove a boxed warning on some formulations.", "s": "high" }, { "t": "Fluid restriction is mandatory, not advisory", "d": "Patients must limit fluid intake around dosing. Failure to do so is the usual route to severe hyponatremia.", "s": "high" }, { "t": "Elderly patients are markedly higher risk", "d": "Age-related reduction in free water clearance makes hyponatremia both more likely and more dangerous; some formulations are not recommended over 65.", "s": "high" }, { "t": "Tachyphylaxis in haemostatic use", "d": "Stored von Willebrand factor is depleted after repeated doses, so the haemostatic effect fades within 2–3 doses.", "s": "moderate" }, { "t": "Thrombotic events reported", "d": "Rare arterial thrombotic events have been reported with haemostatic use in patients with cardiovascular risk.", "s": "moderate" }, { "t": "Ineffective in nephrogenic diabetes insipidus", "d": "The defect is receptor-level, so supplying more hormone does nothing.", "s": "moderate" }, { "t": "Nasal formulation variability", "d": "Absorption varies with rhinitis and technique; some nasal products were withdrawn over dosing inconsistency.", "s": "moderate" } ], "avoid": [ "Hyponatremia or history of hyponatremia", "Moderate to severe renal impairment", "SIADH", "Uncontrolled heart failure", "Polydipsia", "Concurrent loop diuretics or SSRIs (relative — both raise hyponatremia risk)" ], "monitoring": [ "Serum sodium before starting, within the first week, then periodically — non-negotiable in older adults", "Fluid intake around dosing", "Weight and oedema", "Factor VIII and von Willebrand factor levels for haemostatic use" ], "legal": "Prescription drug across all formulations.", "evidenceNotes": [ "Decades of trials across several distinct indications, each with its own evidence base and its own risk profile." ], "interactions": [ "SSRIs, tricyclics, carbamazepine, chlorpropamide — all increase hyponatremia risk", "NSAIDs — increase antidiuretic effect and hyponatremia risk", "Loop diuretics — compound sodium disturbance", "Glucocorticoids — reduce effect" ], "confusedWith": [ { "slug": "oxytocin", "why": "Oxytocin and vasopressin differ by only two amino acids, which is why high-dose oxytocin causes water retention and hyponatremia. Desmopressin is the engineered vasopressin analog; the two are not interchangeable." } ], "tags": [ "diabetes insipidus", "bleeding disorders", "nocturia", "vasopressin", "approved" ] }, { "slug": "dihexa", "name": "Dihexa", "aka": [ "N-hexanoic-Tyr-Ile-(6) aminohexanoic amide", "PNB-0408" ], "category": "cognitive", "chemClass": "Angiotensin IV analog — small oligopeptide HGF/c-Met potentiator", "route": "Oral or subcutaneous (research)", "halfLife": "Not established in humans", "status": "research", "statusNote": "Preclinical only. No human trials have been conducted. Not approved anywhere.", "evidence": 1, "summary": "Reported in rodent work to be orders of magnitude more potent than BDNF at forming new synapses. That potency is the reason it attracts attention and the reason it should be treated with unusual caution — a molecule that powerful in the brain with zero human data is not a supplement.", "mechanism": "Potentiates hepatocyte growth factor signalling at the c-Met receptor, driving dendritic spine formation and synaptogenesis in hippocampal neurons. Designed for blood-brain barrier penetration and metabolic stability relative to the parent angiotensin IV peptide.", "studied": "Rodent models of cognitive impairment, including scopolamine-induced deficits and Parkinson models. No human studies at all.", "benefits": [ { "t": "Extremely potent synaptogenesis in vitro", "d": "Reported to promote dendritic spine formation at picomolar to femtomolar concentrations in hippocampal culture.", "s": "preliminary" }, { "t": "Cognitive restoration in rodent models", "d": "Reverses learning deficits in several animal models of cognitive impairment.", "s": "preliminary" }, { "t": "Orally active and CNS-penetrant", "d": "Designed specifically to survive oral administration and cross the blood-brain barrier, unusual for a peptide.", "s": "preliminary" } ], "risks": [ { "t": "No human data of any kind", "d": "Not a single human trial. There is no known safe dose, no known adverse-event profile, and no known interaction set.", "s": "high" }, { "t": "c-Met is an oncogene pathway", "d": "HGF/c-Met signalling is a well-established driver in multiple cancers and a target of oncology drugs designed to block it. Chronically potentiating it is the opposite intervention.", "s": "high" }, { "t": "Uncontrolled synaptic remodelling", "d": "Non-specific synaptogenesis throughout the brain is not obviously desirable and has no precedent in human therapeutics.", "s": "high" }, { "t": "Research-chemical supply", "d": "Purity and identity unverified; some products marketed as dihexa have failed independent analysis.", "s": "high" } ], "avoid": [ "All human use outside a formal clinical trial" ], "monitoring": [ "Not applicable" ], "legal": "Not approved anywhere. Sold under research-use-only labelling.", "evidenceNotes": [ "Preclinical only. The gap between the marketing and the evidence here is among the widest on this site." ], "tags": [ "nootropic", "synaptogenesis", "high risk", "preclinical only" ], "confusedWith": [ { "slug": "davunetide", "why": "Both neuroactive peptides marketed on synaptic mechanisms. Davunetide actually ran a properly powered phase 3 trial and failed. Dihexa has never been given to a human in a published study." } ] }, { "slug": "dsip", "name": "DSIP", "aka": [ "Delta Sleep-Inducing Peptide" ], "category": "other", "chemClass": "Nonapeptide isolated from rabbit cerebral venous blood during induced sleep", "route": "Subcutaneous or intravenous (research)", "halfLife": "Minutes — very rapidly degraded", "status": "research", "statusNote": "Not approved. Studied sporadically since the 1970s without producing a consistent result.", "evidence": 1, "summary": "Named for an effect it has struggled to reproduce. Fifty years after its discovery, the sleep evidence remains inconsistent and the compound has never progressed toward approval anywhere.", "mechanism": "Not well established. Proposed effects on delta-wave sleep, modulation of hypothalamic-pituitary-adrenal axis activity, and interactions with opioid and GABAergic systems. No settled receptor target has been identified.", "studied": "Small human studies in insomnia, chronic pain and opioid withdrawal from the 1970s–1990s, with inconsistent results; sporadic subsequent work.", "benefits": [ { "t": "Some sleep-onset improvement reported", "d": "A minority of small studies reported reduced sleep latency and improved subjective sleep quality.", "s": "preliminary" }, { "t": "Possible stress-axis modulation", "d": "Some studies reported normalisation of cortisol patterns.", "s": "preliminary" }, { "t": "Opioid withdrawal signals", "d": "Small older studies suggested reduced withdrawal symptoms.", "s": "preliminary" }, { "t": "Low reported toxicity", "d": "No significant toxicity signals in the limited studies performed.", "s": "preliminary" } ], "risks": [ { "t": "Inconsistent and largely negative evidence", "d": "Fifty years of intermittent research has not established a reproducible sleep effect.", "s": "high" }, { "t": "Extremely short half-life", "d": "Rapid degradation makes sustained effect from peripheral administration implausible.", "s": "moderate" }, { "t": "No defined mechanism", "d": "Without a known receptor target, dosing and safety cannot be reasoned about.", "s": "moderate" }, { "t": "Unregulated supply", "d": "Research-chemical market.", "s": "high" }, { "t": "Delays proper insomnia treatment", "d": "CBT-I and validated pharmacotherapy have strong evidence; substituting an unvalidated peptide is a real opportunity cost.", "s": "moderate" } ], "avoid": [ "Use in place of evidence-based insomnia treatment", "Pregnancy" ], "monitoring": [ "Sleep diary or actigraphy if used", "Screening for treatable sleep disorders such as apnea" ], "legal": "Not approved for human use.", "evidenceNotes": [ "A long research history that never converged on a reproducible effect." ], "tags": [ "sleep", "insomnia", "research chemical", "weak evidence" ] }, { "slug": "dulaglutide", "name": "Dulaglutide", "aka": [ "Trulicity" ], "category": "metabolic", "chemClass": "GLP-1 analog fused to a modified human IgG4 Fc fragment", "route": "Subcutaneous, once weekly", "halfLife": "~5 days", "status": "approved", "statusNote": "FDA-approved for type 2 diabetes and for cardiovascular risk reduction in type 2 diabetes.", "evidence": 5, "summary": "A GLP-1 molecule bolted onto an antibody fragment to slow its clearance — a different half-life strategy from the fatty-acid acylation used by semaglutide. Its distinguishing evidence is the REWIND trial, which showed cardiovascular benefit in a mostly primary-prevention population.", "mechanism": "GLP-1 receptor agonism. Covalent fusion to an IgG4 Fc fragment increases molecular size above the renal filtration threshold and engages FcRn recycling, extending half-life to permit weekly dosing.", "studied": "AWARD program in type 2 diabetes; REWIND cardiovascular outcomes trial.", "benefits": [ { "t": "Cardiovascular benefit in primary prevention", "d": "REWIND is distinctive: most participants had no established cardiovascular disease at baseline, and benefit was still demonstrated.", "s": "strong" }, { "t": "Reliable glycemic control", "d": "HbA1c reductions of roughly 1.4–1.6 percentage points across the AWARD trials.", "s": "strong" }, { "t": "Simple delivery device", "d": "A hidden-needle autoinjector with no dose dialling or priming, which measurably improves adherence in less dexterous patients.", "s": "moderate" }, { "t": "Kidney outcome signals", "d": "Exploratory REWIND analyses showed reduced progression of albuminuria.", "s": "moderate" } ], "risks": [ { "t": "Modest weight loss", "d": "Around 3 kg on average — far less than semaglutide or tirzepatide. It is a glycemic drug that also reduces weight, not a weight-loss drug.", "s": "moderate" }, { "t": "Thyroid C-cell boxed warning", "d": "Standard class contraindication for medullary thyroid carcinoma and MEN2.", "s": "high" }, { "t": "GI adverse effects", "d": "Nausea, diarrhea and vomiting, most common during titration.", "s": "moderate" }, { "t": "Pancreatitis and gallbladder disease", "d": "Class effects.", "s": "high" }, { "t": "No weight-management indication", "d": "It is not approved for obesity, and prescribing it for that purpose is off-label.", "s": "low" } ], "avoid": [ "Medullary thyroid carcinoma or MEN2 history", "Pregnancy", "Prior pancreatitis (relative)", "Type 1 diabetes" ], "monitoring": [ "HbA1c, weight", "Renal function during GI illness", "Concomitant insulin dosing" ], "legal": "Prescription drug.", "evidenceNotes": [ "REWIND is the strongest primary-prevention cardiovascular evidence in the GLP-1 class." ], "interactions": [ "Insulin and sulfonylureas — dose reduction usually needed", "Oral drugs sensitive to gastric emptying" ], "tags": [ "diabetes", "GLP-1", "cardiovascular", "approved", "weekly" ] }, { "slug": "elamipretide", "name": "Elamipretide (SS-31)", "aka": [ "SS-31", "MTP-131", "Bendavia", "Forzinity" ], "category": "longevity", "chemClass": "Cardiolipin-targeting mitochondrial tetrapeptide", "route": "Subcutaneous", "halfLife": "~2–4 hours", "status": "limited", "statusNote": "Approved in the US for Barth syndrome, an ultra-rare mitochondrial disorder. Trials in primary mitochondrial myopathy and dry AMD did not meet primary endpoints.", "evidence": 4, "summary": "The most rigorously developed mitochondrial peptide, and a case study in how a real drug development program plays out: an approval in one ultra-rare disease, and several failed trials in the larger indications people actually want it for.", "mechanism": "Concentrates in the inner mitochondrial membrane where it binds cardiolipin, stabilising cristae architecture and the electron transport chain supercomplexes. This improves ATP production efficiency and reduces electron leak and reactive oxygen species generation.", "studied": "Phase 3 trials in primary mitochondrial myopathy (MMPOWER-3), Barth syndrome (TAZPOWER and extension), dry age-related macular degeneration, and heart failure.", "benefits": [ { "t": "Approved for Barth syndrome", "d": "Regulatory approval based on functional improvement data in an ultra-rare mitochondrial cardiomyopathy — a real clinical result.", "s": "strong" }, { "t": "Well-defined molecular mechanism", "d": "Cardiolipin binding and cristae stabilisation are directly demonstrable, unlike most \"mitochondrial support\" claims.", "s": "strong" }, { "t": "Improved muscle strength signals", "d": "Extension studies in Barth syndrome showed progressive improvement in muscle strength measures over long-term dosing.", "s": "moderate" }, { "t": "Extensive safety database", "d": "Years of exposure across multiple trial programs.", "s": "strong" } ], "risks": [ { "t": "Failed its largest trials", "d": "Did not meet the primary endpoint in primary mitochondrial myopathy or in dry AMD. Broad \"mitochondrial health\" benefit is not supported.", "s": "high" }, { "t": "Injection-site reactions", "d": "The most common adverse event, occurring in a majority of patients in some trials.", "s": "moderate" }, { "t": "Very narrow approved indication", "d": "Any use outside Barth syndrome is off-label and unsupported by positive trial data.", "s": "moderate" }, { "t": "Cost and access", "d": "Ultra-orphan drug pricing; not realistically accessible for wellness use.", "s": "low" }, { "t": "Grey-market SS-31", "d": "\"SS-31\" sold as a research peptide is not the pharmaceutical product and carries no quality assurance.", "s": "high" } ], "avoid": [ "Off-label use for general anti-aging — the trials that tested broader benefit were negative", "Pregnancy (insufficient data)" ], "monitoring": [ "Injection-site assessment", "Disease-specific functional measures" ], "legal": "Approved for a single ultra-rare indication. Research-grade \"SS-31\" is a separate, unapproved product.", "evidenceNotes": [ "Multiple phase 3 trials — a genuinely rigorous program, including informative negative results." ], "tags": [ "mitochondria", "rare disease", "cardiolipin", "approved", "failed trials" ], "confusedWith": [ { "slug": "mots-c", "why": "Both marketed as mitochondrial peptides. Elamipretide completed multiple phase 3 trials and holds an approval for one ultra-rare disease; MOTS-c has never been given to humans in a controlled trial." } ] }, { "slug": "epitalon", "name": "Epitalon", "aka": [ "Epithalon", "AEDG peptide", "Ala-Glu-Asp-Gly" ], "category": "longevity", "chemClass": "Synthetic tetrapeptide modelled on the pineal extract epithalamin", "route": "Subcutaneous or intranasal (research)", "halfLife": "Very short — minutes", "status": "research", "statusNote": "Not approved in the US, EU or UK. Used in Russian gerontology practice. Widely sold as an anti-aging research peptide.", "evidence": 2, "summary": "The flagship \"longevity peptide\", built on decades of work by a single Russian research group reporting telomerase activation and reduced mortality. The claims are extraordinary; the independent replication is absent.", "mechanism": "Proposed to induce telomerase reverse transcriptase expression, lengthening telomeres in cultured cells, and to normalise pineal melatonin rhythm and neuroendocrine function. Some work suggests direct interaction with promoter regions of specific genes.", "studied": "Russian studies in elderly cohorts reporting reduced mortality over multi-year follow-up; cell culture telomerase work; rodent lifespan studies.", "benefits": [ { "t": "Telomerase activation in cell culture", "d": "Reported induction of telomerase and telomere elongation in human somatic cell cultures — the core scientific claim.", "s": "preliminary" }, { "t": "Melatonin rhythm normalisation", "d": "Studies report restored nocturnal melatonin secretion in older subjects, with corresponding sleep improvements.", "s": "preliminary" }, { "t": "Reduced mortality in Russian cohort studies", "d": "Long-term follow-up studies reported lower mortality in treated elderly groups. Methodology and independence are significant caveats.", "s": "preliminary" }, { "t": "Antioxidant effects in animal models", "d": "Reduced lipid peroxidation and improved antioxidant enzyme activity in rodents.", "s": "preliminary" } ], "risks": [ { "t": "No independent replication", "d": "Nearly all supporting work traces to one research group. Extraordinary claims with a single source are not established findings.", "s": "high" }, { "t": "Telomerase activation and cancer", "d": "Telomerase reactivation is a hallmark of most cancers. A drug designed to switch it on systemically has an obvious and unstudied oncologic concern.", "s": "high" }, { "t": "No Western trials", "d": "No FDA or EMA review; no registered trials with contemporary methodology.", "s": "high" }, { "t": "Unregulated supply", "d": "Sold as a research chemical with no purity assurance.", "s": "high" }, { "t": "No established safe dosing", "d": "Protocols circulating online have no clinical validation.", "s": "moderate" } ], "avoid": [ "Any cancer history or active malignancy", "Pregnancy", "Anyone unwilling to accept entirely unquantified long-term risk" ], "monitoring": [ "No validated monitoring; age-appropriate cancer screening is prudent for anyone considering it" ], "legal": "Not approved for human use in the US, EU or UK.", "evidenceNotes": [ "Single-group evidence base with high-stakes unreplicated claims." ], "tags": [ "longevity", "telomerase", "pineal", "research chemical", "unreplicated" ], "confusedWith": [ { "slug": "thymalin", "why": "Both come from the same Russian gerontology research tradition and are sold together as an anti-aging pair. Neither has independent replication outside that tradition." } ] }, { "slug": "exenatide", "name": "Exenatide", "aka": [ "Byetta", "Bydureon", "exendin-4" ], "category": "metabolic", "chemClass": "GLP-1 receptor agonist — synthetic exendin-4, from Gila monster venom", "route": "Subcutaneous twice daily, or extended-release weekly", "halfLife": "~2.4 hours (immediate release)", "status": "approved", "statusNote": "FDA-approved for type 2 diabetes (2005). Several formulations have since been discontinued commercially.", "evidence": 5, "summary": "The first GLP-1 agonist ever approved, and a genuinely strange origin story: it is a near-copy of a peptide in Gila monster saliva that happens to resist the enzyme that destroys human GLP-1 within minutes. Every drug in this class descends from that observation.", "mechanism": "Exendin-4 shares roughly 53% sequence identity with human GLP-1 but lacks the DPP-4 cleavage site, so it survives in circulation long enough to be a drug. It produces the same glucose-dependent insulin secretion, glucagon suppression and delayed gastric emptying.", "studied": "AMIGO trials in type 2 diabetes; EXSCEL cardiovascular outcomes trial; DURATION program for the extended-release formulation.", "benefits": [ { "t": "Established glycemic efficacy", "d": "HbA1c reductions around 1 percentage point, with weight loss rather than weight gain — the finding that reshaped diabetes care.", "s": "strong" }, { "t": "Cardiovascular safety demonstrated", "d": "The EXSCEL trial confirmed cardiovascular safety, though it did not show the superiority later seen with semaglutide and liraglutide.", "s": "strong" }, { "t": "Two decades of safety data", "d": "The longest real-world record of any GLP-1 agonist.", "s": "strong" }, { "t": "Proof of concept for the class", "d": "Its success created the pathway that led to semaglutide and tirzepatide.", "s": "strong" } ], "risks": [ { "t": "Superseded on efficacy", "d": "Weight loss and glycemic effects are substantially smaller than newer agents. There is little reason to start it today.", "s": "moderate" }, { "t": "Twice-daily injection", "d": "The immediate-release formulation is the most burdensome regimen in the class.", "s": "low" }, { "t": "Renal impairment cautions", "d": "Not recommended in severe renal impairment; acute kidney injury has been reported, often with dehydration from GI effects.", "s": "high" }, { "t": "Injection-site nodules with extended release", "d": "The microsphere formulation commonly causes persistent subcutaneous nodules.", "s": "moderate" }, { "t": "Antibody formation", "d": "Anti-exenatide antibodies develop in a substantial fraction of users and can reduce efficacy — a problem specific to this non-human sequence.", "s": "moderate" }, { "t": "Pancreatitis reports", "d": "Class effect; uncommon but serious.", "s": "high" } ], "avoid": [ "Severe renal impairment (eGFR under 30)", "Prior pancreatitis (relative)", "Pregnancy", "Medullary thyroid carcinoma history (extended-release formulation)" ], "monitoring": [ "HbA1c, weight", "Renal function, particularly during GI illness", "Injection sites" ], "legal": "Prescription drug; commercial availability of individual formulations has narrowed.", "evidenceNotes": [ "Two decades of trials and post-marketing data.", "Its cardiovascular trial was neutral, not positive — a useful contrast with semaglutide." ], "interactions": [ "Warfarin — INR monitoring advised", "Oral antibiotics and contraceptives — take at least 1 hour before exenatide", "Insulin and sulfonylureas — hypoglycemia risk" ], "tags": [ "diabetes", "GLP-1", "first-in-class", "Gila monster", "approved" ] }, { "slug": "follistatin-344", "name": "Follistatin-344", "aka": [ "FST-344", "myostatin inhibitor" ], "category": "other", "chemClass": "Recombinant follistatin isoform — an activin and myostatin-binding glycoprotein", "route": "Subcutaneous (research); gene therapy in trials", "halfLife": "Very short as a protein — minutes to hours", "status": "research", "statusNote": "Not approved. Follistatin gene therapy has been studied in muscular dystrophy trials; injectable recombinant follistatin has not been developed for human use.", "evidence": 1, "summary": "Myostatin inhibition produces the double-muscled cattle phenotype, and follistatin is one way to achieve it. The gene therapy work in muscular dystrophy is legitimate. The injectable version sold to bodybuilders is not the same intervention and has essentially no supporting data.", "mechanism": "Binds and neutralises myostatin (GDF-8) and activins, removing the brake on skeletal muscle growth. Activin signalling also regulates reproduction, inflammation and tissue fibrosis, so blocking it has effects well beyond muscle.", "studied": "AAV-delivered follistatin gene therapy phase 1/2 trials in Becker muscular dystrophy and inclusion body myositis; extensive animal work. No trials of injectable recombinant follistatin.", "benefits": [ { "t": "Dramatic muscle growth in animal models", "d": "Follistatin overexpression produces substantial and sustained muscle hypertrophy in mice and non-human primates.", "s": "preliminary" }, { "t": "Gene therapy signals in muscular dystrophy", "d": "Small early-phase trials reported improved 6-minute walk distance and muscle histology.", "s": "preliminary" }, { "t": "Antifibrotic activity", "d": "Activin blockade reduces fibrosis in preclinical models of muscle and organ disease.", "s": "preliminary" } ], "risks": [ { "t": "Injectable form is unstudied in humans", "d": "The trial evidence is for gene therapy — a completely different intervention with different pharmacology.", "s": "high" }, { "t": "Activin blockade affects multiple systems", "d": "Reproductive function, inflammatory regulation and tissue repair all depend on activin signalling.", "s": "high" }, { "t": "Tendon-muscle mismatch injury", "d": "Muscle hypertrophy outpacing tendon adaptation is a documented injury mechanism in myostatin-inhibited animals.", "s": "moderate" }, { "t": "Cardiac muscle effects unknown", "d": "Myostatin is expressed in cardiac tissue; consequences of chronic inhibition in the heart are not characterised.", "s": "high" }, { "t": "Very poor bioavailability", "d": "Rapid clearance makes injected recombinant follistatin unlikely to achieve meaningful sustained effect regardless.", "s": "moderate" }, { "t": "Extremely expensive and frequently counterfeit", "d": "Genuine recombinant follistatin is costly; grey-market products are often not what they claim.", "s": "high" } ], "avoid": [ "All non-trial human use", "Cancer history — activin signalling is involved in tumour suppression" ], "monitoring": [ "Not applicable" ], "legal": "Not approved for human use.", "evidenceNotes": [ "Legitimate gene therapy research; the injectable consumer product is unrelated to it." ], "tags": [ "muscle", "myostatin", "gene therapy", "research chemical", "high risk" ], "confusedWith": [ { "slug": "gdf-11", "why": "Follistatin blocks myostatin and activins to increase muscle. GDF-11 is myostatin-like and may reduce it. They are sold adjacently but may act in opposite directions." } ] }, { "slug": "foxo4-dri", "name": "FOXO4-DRI", "aka": [ "FOXO4-p53 interfering peptide" ], "category": "longevity", "chemClass": "Retro-inverso D-amino acid peptide targeting the FOXO4-p53 interaction", "route": "Intravenous or intraperitoneal (research)", "halfLife": "Extended relative to L-peptides due to D-amino acid composition", "status": "research", "statusNote": "Preclinical senolytic research compound. No human trials. Not approved.", "evidence": 1, "summary": "A designed senolytic that kills senescent cells by disrupting the protein interaction keeping them alive. The mouse results — restored fur density, improved renal function, recovered fitness in aged animals — are among the most visually striking in aging research. There is no human data.", "mechanism": "Senescent cells sequester p53 in the nucleus via FOXO4 to avoid apoptosis. This retro-inverso peptide competitively disrupts that interaction, releasing p53 and triggering apoptosis selectively in senescent cells while sparing healthy ones.", "studied": "Mouse studies in naturally aged, fast-aging (Xpd) and chemotherapy-treated animals. No human studies.", "benefits": [ { "t": "Selective senescent cell clearance in mice", "d": "Demonstrated targeted apoptosis of senescent cells with sparing of normal cells in animal models.", "s": "preliminary" }, { "t": "Reversal of aging phenotypes in mice", "d": "Restored fur density, renal function and physical fitness in aged mice — a landmark preclinical result.", "s": "preliminary" }, { "t": "D-amino acid stability", "d": "Retro-inverso design resists proteolysis, addressing a common peptide limitation.", "s": "preliminary" } ], "risks": [ { "t": "No human data at all", "d": "Not one human has been dosed in a published trial. Nothing is known about human safety.", "s": "high" }, { "t": "p53 activation is a blunt instrument", "d": "Releasing p53 broadly can trigger apoptosis in stressed but healthy cells; the selectivity margin in humans is unknown.", "s": "high" }, { "t": "Senescent cells have useful functions", "d": "They participate in wound healing and tumour suppression; indiscriminate clearance is not automatically beneficial.", "s": "high" }, { "t": "Complex and expensive synthesis", "d": "Products sold cheaply online are unlikely to be the actual compound at meaningful purity.", "s": "high" } ], "avoid": [ "All human use outside a formal clinical trial" ], "monitoring": [ "Not applicable" ], "legal": "Not approved anywhere.", "evidenceNotes": [ "Landmark mouse study; no clinical translation." ], "tags": [ "senolytic", "longevity", "p53", "preclinical only", "high risk" ] }, { "slug": "gdf-11", "name": "GDF-11", "aka": [ "Growth Differentiation Factor 11", "BMP-11" ], "category": "longevity", "chemClass": "TGF-beta superfamily protein, closely homologous to myostatin (GDF-8)", "route": "Intraperitoneal or subcutaneous (research)", "halfLife": "Short; circulates bound to latency proteins", "status": "research", "statusNote": "Preclinical research protein. No human trials. Not approved. Its central claims are scientifically contested.", "evidence": 1, "summary": "The most publicly contested molecule in aging research. A 2013 paper reported that GDF-11 declines with age and that restoring it rejuvenates heart, muscle and brain in mice. Subsequent work from other groups found the opposite on several points, including the direction of the age-related change.", "mechanism": "Signals through activin type II receptors and SMAD2/3, sharing roughly 90% sequence identity with myostatin in its mature domain. That homology is central to the controversy: assays that could not distinguish GDF-11 from myostatin were used in the original work.", "studied": "Mouse parabiosis and supplementation studies with directly conflicting results across laboratories. No human interventional trials.", "benefits": [ { "t": "Reported cardiac rejuvenation in mice", "d": "The original work described reversal of age-related cardiac hypertrophy in aged mice given GDF-11.", "s": "preliminary" }, { "t": "Reported neurogenesis and vascular effects", "d": "Follow-up work from the same group described improved cerebral vasculature and neurogenesis.", "s": "preliminary" }, { "t": "Genuine developmental role", "d": "GDF-11 is unambiguously important in embryonic axial patterning — that part is not disputed.", "s": "moderate" } ], "risks": [ { "t": "Core findings contested by independent groups", "d": "Other laboratories reported that GDF-11 does not decline with age, and that supplementation inhibits rather than promotes muscle regeneration. This is an active scientific dispute, not settled science.", "s": "high" }, { "t": "Assay cross-reactivity problem", "d": "Because GDF-11 and myostatin are so similar, several early measurements may have been detecting myostatin instead.", "s": "high" }, { "t": "Muscle atrophy in some studies", "d": "Given the myostatin homology, GDF-11 may suppress muscle growth — the opposite of what the anti-aging framing implies.", "s": "high" }, { "t": "Cachexia signals", "d": "High GDF-11 levels have been associated with frailty and cachexia in some human observational work.", "s": "high" }, { "t": "No human data", "d": "No trials, no dosing, no safety characterisation.", "s": "high" }, { "t": "Sold as a research chemical", "d": "Marketed on the strength of the disputed 2013 findings, with the contradicting literature unmentioned.", "s": "high" } ], "avoid": [ "All human use — the underlying science is unresolved and the direction of effect is disputed" ], "monitoring": [ "Not applicable" ], "legal": "Not approved for human use.", "evidenceNotes": [ "A genuine and unresolved scientific controversy. Any source presenting the rejuvenation claims as established is not describing the current literature." ], "confusedWith": [ { "slug": "follistatin-344", "why": "Follistatin inhibits myostatin and activins to increase muscle. GDF-11 is myostatin-like and may reduce it. They are marketed adjacently but may act in opposite directions." } ], "tags": [ "longevity", "contested science", "myostatin", "parabiosis", "preclinical only" ] }, { "slug": "ghk-cu", "name": "GHK-Cu", "aka": [ "Copper tripeptide-1", "Gly-His-Lys copper complex" ], "category": "cosmetic", "chemClass": "Naturally occurring copper-binding tripeptide", "route": "Topical (well studied); injectable (not studied)", "halfLife": "Topical residence measured in hours; declines with age in plasma", "status": "cosmetic", "statusNote": "Established cosmetic ingredient with human topical data. Injectable use is unapproved and unstudied.", "evidence": 3, "summary": "One of the few peptides on this list with credible controlled human data — for skin, applied topically. It occurs naturally in plasma, declining roughly 60% between age 20 and 60, which is the origin of its anti-aging framing.", "mechanism": "Chelates copper(II) and delivers it to cells, modulating expression of a broad set of genes involved in extracellular matrix remodelling. Stimulates collagen I, elastin, glycosaminoglycan and proteoglycan synthesis while modulating metalloproteinase activity, and has antioxidant and anti-inflammatory effects.", "studied": "Multiple controlled topical trials in facial photoaging, wound healing, and hair growth; extensive fibroblast and gene-expression work.", "benefits": [ { "t": "Improved skin firmness and wrinkle depth", "d": "Controlled facial trials with copper-peptide creams showed measurable improvements in wrinkle depth, skin density and elasticity versus vehicle.", "s": "moderate" }, { "t": "Wound healing acceleration", "d": "Human and animal studies show faster closure and better-organised collagen deposition in wounds.", "s": "moderate" }, { "t": "Collagen and elastin stimulation", "d": "Robust fibroblast data showing upregulation of matrix synthesis.", "s": "moderate" }, { "t": "Hair follicle effects", "d": "Small studies suggest increased follicle size and hair density with topical application.", "s": "preliminary" }, { "t": "Antioxidant and anti-inflammatory activity", "d": "Reduces oxidative damage markers in laboratory models.", "s": "preliminary" } ], "risks": [ { "t": "Injectable use has no evidence base", "d": "The credible data is topical. Injecting copper peptides for systemic anti-aging has not been studied and introduces copper-load questions.", "s": "high" }, { "t": "Copper accumulation concern", "d": "Chronic high-dose systemic copper exposure carries hepatic and neurologic risk; contraindicated in Wilson disease.", "s": "moderate" }, { "t": "Skin irritation and contact dermatitis", "d": "Occurs in a minority of topical users, more often at higher concentrations.", "s": "low" }, { "t": "Incompatibility with vitamin C and some acids", "d": "Direct co-application can destabilise the complex; separate application times are advised.", "s": "low" }, { "t": "Wide variation in product concentration", "d": "Cosmetic products differ enormously in actual GHK-Cu content and formulation quality.", "s": "moderate" } ], "avoid": [ "Wilson disease or copper metabolism disorders (systemic use)", "Known copper allergy", "Broken or actively infected skin without medical advice" ], "monitoring": [ "Topical use: none required", "Systemic use: not advised outside research" ], "legal": "Lawful as a cosmetic ingredient. Injectable preparations are unapproved.", "evidenceNotes": [ "Among the better-supported peptides for topical use.", "Systemic evidence is essentially absent — do not conflate the two." ], "tags": [ "skin", "collagen", "topical", "hair", "wound healing" ], "confusedWith": [ { "slug": "palmitoyl-tripeptide-1", "why": "Same GHK tripeptide. GHK-Cu carries a copper ion and works partly by delivering copper; palmitoyl tripeptide-1 carries a fatty tail for penetration and delivers no copper." } ] }, { "slug": "ghrp-2", "name": "GHRP-2", "aka": [ "Pralmorelin", "KP-102" ], "category": "growth", "chemClass": "Growth hormone-releasing peptide — synthetic hexapeptide ghrelin mimetic", "route": "Subcutaneous or intravenous", "halfLife": "~30–60 minutes", "status": "limited", "statusNote": "Approved in Japan as a diagnostic agent for GH deficiency. Not approved in the US or EU for therapeutic use.", "evidence": 3, "summary": "A potent GH secretagogue with a genuine regulatory approval — but as a single-dose pituitary function test, not as a therapy. Its therapeutic use is entirely off-label extrapolation.", "mechanism": "Ghrelin receptor agonism at the pituitary and hypothalamus. More potent than ipamorelin at releasing GH, but less selective: it produces measurable rises in ACTH, cortisol and prolactin.", "studied": "Diagnostic validation studies in Japan; short-term GH secretion studies; small studies in cachexia.", "benefits": [ { "t": "Strong, reliable GH release", "d": "Robust and reproducible enough to serve as an approved diagnostic stimulus for pituitary function.", "s": "strong" }, { "t": "Appetite stimulation", "d": "Meaningful in cachexia and appetite-loss settings, where it has been studied in small trials.", "s": "preliminary" }, { "t": "Oral and intranasal bioavailability studied", "d": "Alternative routes have been explored, unlike most peptides.", "s": "preliminary" } ], "risks": [ { "t": "Cortisol and prolactin elevation", "d": "Less selective than ipamorelin; repeated dosing can push these hormones outside normal ranges.", "s": "moderate" }, { "t": "No therapeutic approval", "d": "Approved only as a one-off diagnostic; chronic dosing has never been evaluated for safety.", "s": "high" }, { "t": "Tachyphylaxis", "d": "GH response declines with continued use.", "s": "moderate" }, { "t": "Insulin resistance", "d": "GH-axis class effect.", "s": "moderate" }, { "t": "Unregulated supply outside Japan", "d": "Sold as a research chemical with no quality assurance.", "s": "high" }, { "t": "Banned in sport", "d": "Prohibited by WADA.", "s": "low" } ], "avoid": [ "Active malignancy", "Pregnancy", "Hyperprolactinemia", "Cushing syndrome or adrenal disorder" ], "monitoring": [ "IGF-1, prolactin, morning cortisol", "Fasting glucose" ], "legal": "Diagnostic approval in Japan only. Not lawful for therapeutic sale in the US.", "evidenceNotes": [ "Good acute pharmacology data; essentially no chronic-use safety data." ], "tags": [ "growth hormone", "ghrelin", "diagnostic", "appetite" ] }, { "slug": "ghrp-6", "name": "GHRP-6", "aka": [ "Growth Hormone Releasing Hexapeptide" ], "category": "growth", "chemClass": "First-generation growth hormone-releasing hexapeptide", "route": "Subcutaneous (research)", "halfLife": "~15–60 minutes", "status": "research", "statusNote": "Not approved. Superseded by more selective secretagogues; largely of historical and research interest.", "evidence": 2, "summary": "The compound that opened up the whole GHS field — it led directly to the discovery of the ghrelin receptor. As a therapy it is crude: powerful hunger stimulation and hormonal cross-talk made it impractical.", "mechanism": "Ghrelin receptor agonism with substantial off-target activation of ACTH/cortisol and prolactin release, plus strong central appetite stimulation.", "studied": "Extensive endocrine pharmacology research; small cardioprotection studies; no completed therapeutic development program.", "benefits": [ { "t": "Powerful appetite stimulation", "d": "Among the strongest orexigenic effects of any peptide — potentially useful in cachexia, and unwanted in almost every other context.", "s": "moderate" }, { "t": "Reliable GH release", "d": "Effective as a pituitary stimulus, historically important for characterising the GH axis.", "s": "moderate" }, { "t": "Preclinical cytoprotective signals", "d": "Animal work suggests cardioprotective and gastric-protective effects.", "s": "preliminary" } ], "risks": [ { "t": "Intense hunger", "d": "Often sabotages the body-composition goals people take it for.", "s": "moderate" }, { "t": "Cortisol and prolactin elevation", "d": "More pronounced than with newer secretagogues; chronic elevation carries real endocrine consequences.", "s": "moderate" }, { "t": "No approved use anywhere", "d": "Never completed clinical development.", "s": "high" }, { "t": "Rapid desensitisation", "d": "Response falls off with repeated dosing.", "s": "moderate" }, { "t": "Unregulated supply", "d": "Research-chemical market only.", "s": "high" }, { "t": "WADA prohibited", "d": "Banned at all times in tested sport.", "s": "low" } ], "avoid": [ "Active malignancy", "Pregnancy", "Hyperprolactinemia", "Diabetes" ], "monitoring": [ "IGF-1, prolactin, cortisol", "Glucose" ], "legal": "Not approved for human use in any major market.", "evidenceNotes": [ "Historically important research tool; no therapeutic evidence base." ], "tags": [ "growth hormone", "ghrelin", "appetite", "research chemical" ] }, { "slug": "glutathione", "name": "Glutathione", "aka": [ "GSH", "L-glutathione" ], "category": "other", "chemClass": "Endogenous tripeptide antioxidant (glutamate-cysteine-glycine)", "route": "Oral, intravenous, liposomal, inhaled", "halfLife": "Minutes intravenously", "status": "research", "statusNote": "A lawful oral supplement. Injectable glutathione for skin lightening is unapproved; FDA has warned against imported injectable products.", "evidence": 2, "summary": "The body's principal intracellular antioxidant, and an entirely legitimate molecule with a largely illegitimate injectable market. Oral supplementation faces a real bioavailability problem; IV skin-lightening infusions face a real safety problem.", "mechanism": "Central redox buffer neutralising reactive oxygen species and supporting phase II hepatic detoxification via glutathione S-transferases. The skin-lightening claim rests on inhibition of tyrosinase and a shift from eumelanin toward pheomelanin production.", "studied": "Oral bioavailability studies; small trials of oral glutathione for skin lightening; N-acetylcysteine (a precursor) has far better clinical evidence; no rigorous trials of IV glutathione infusion for cosmetic use.", "benefits": [ { "t": "Essential endogenous antioxidant", "d": "Its physiological importance is not in question — depletion is associated with oxidative stress in many disease states.", "s": "strong" }, { "t": "Supports hepatic detoxification", "d": "Central to phase II conjugation; the basis of N-acetylcysteine's use as the antidote in acetaminophen overdose.", "s": "strong" }, { "t": "Modest skin-lightening signal orally", "d": "Small randomized trials of oral glutathione showed measurable reductions in melanin index over several weeks.", "s": "preliminary" }, { "t": "Better raised via precursors", "d": "N-acetylcysteine and whey protein reliably raise intracellular glutathione and have far better evidence than direct supplementation.", "s": "moderate" } ], "risks": [ { "t": "IV skin-lightening infusions are unapproved and unsafe", "d": "FDA and several national regulators have warned against them following reports of severe adverse events including Stevens-Johnson syndrome, renal dysfunction and thyroid effects.", "s": "high" }, { "t": "Poor oral bioavailability", "d": "Standard oral glutathione is largely degraded in the gut; much of the supplement market ignores this.", "s": "moderate" }, { "t": "Infection risk from unregulated infusion clinics", "d": "Non-sterile compounding and IV administration in non-medical settings has caused serious infections.", "s": "high" }, { "t": "Antioxidant supplementation is not uniformly beneficial", "d": "High-dose antioxidants can blunt exercise adaptation and, in some trial contexts, have shown harm.", "s": "moderate" }, { "t": "Skin-lightening motives and safety", "d": "The cosmetic driver of this market pushes people toward high-risk unregulated products.", "s": "moderate" } ], "avoid": [ "IV glutathione for cosmetic purposes", "Asthma (inhaled forms have triggered bronchospasm)", "Pregnancy for injectable use" ], "monitoring": [ "Renal and hepatic function if using injectable forms", "Skin examination" ], "legal": "Lawful as an oral supplement. Injectable cosmetic use is unapproved and subject to import alerts.", "evidenceNotes": [ "Strong physiology, weak supplementation evidence, and a genuinely hazardous injectable market." ], "tags": [ "antioxidant", "skin lightening", "detoxification", "supplement" ], "confusedWith": [ { "slug": "ghk-cu", "why": "Both marketed for skin, both frequently offered by IV infusion clinics. Neither has evidence supporting intravenous cosmetic use, and IV glutathione has specific regulator warnings against it." } ] }, { "slug": "gonadorelin", "name": "Gonadorelin", "aka": [ "GnRH", "LHRH", "Factrel" ], "category": "hormonal", "chemClass": "Synthetic gonadotropin-releasing hormone — decapeptide identical to the endogenous hormone", "route": "Subcutaneous or intravenous", "halfLife": "~2–10 minutes", "status": "limited", "statusNote": "Historically FDA-approved as a diagnostic (Factrel, since discontinued in the US). Now widely supplied through compounding pharmacies for testicular support during testosterone therapy.", "evidence": 3, "summary": "The natural hypothalamic hormone itself. Its modern popularity comes from men on testosterone therapy using it to maintain testicular function — a use with a coherent physiological rationale but limited comparative trial evidence against the better-established hCG.", "mechanism": "Binds pituitary GnRH receptors to stimulate LH and FSH release. The critical detail is pulsatility: intermittent dosing stimulates the axis, while continuous exposure downregulates receptors and suppresses it — the mechanism behind GnRH agonist chemical castration.", "studied": "Historic diagnostic validation studies; pulsatile pump therapy for hypogonadotropic hypogonadism; limited data in the TRT-adjunct context where it is now mostly used.", "benefits": [ { "t": "Maintains testicular function during TRT", "d": "By preserving LH signalling it can limit testicular atrophy and preserve some intratesticular testosterone during exogenous testosterone therapy.", "s": "preliminary" }, { "t": "Fertility restoration in hypogonadotropic hypogonadism", "d": "Pulsatile pump delivery has established efficacy for inducing spermatogenesis and ovulation in this specific condition.", "s": "strong" }, { "t": "Diagnostic utility", "d": "Distinguishes hypothalamic from pituitary causes of hypogonadism.", "s": "strong" }, { "t": "Shorter half-life than hCG", "d": "More physiological pulsatile stimulation and less risk of sustained estradiol elevation than hCG.", "s": "preliminary" } ], "risks": [ { "t": "Paradoxical suppression with incorrect dosing", "d": "Too-frequent or continuous administration downregulates the axis and achieves the opposite of the intended effect. Pulsatility is not optional.", "s": "high" }, { "t": "Limited comparative evidence in TRT use", "d": "The popular indication is supported mostly by physiology and clinical experience, not head-to-head trials against hCG.", "s": "moderate" }, { "t": "Requires an intact pituitary", "d": "Ineffective if the deficiency is pituitary rather than hypothalamic.", "s": "moderate" }, { "t": "Compounding quality variation", "d": "US supply is entirely compounded; potency and sterility vary by pharmacy.", "s": "moderate" }, { "t": "Injection-site reactions and headache", "d": "Common and generally minor.", "s": "low" }, { "t": "Ovarian hyperstimulation in women", "d": "A risk when used for ovulation induction without monitoring.", "s": "high" } ], "avoid": [ "Hormone-sensitive malignancy", "Pregnancy", "Unsupervised use without hormonal monitoring" ], "monitoring": [ "Total and free testosterone, LH, FSH, estradiol", "Semen analysis if fertility is the goal", "Hematocrit if on concurrent TRT" ], "legal": "No approved US product; lawful access is via patient-specific compounding under prescription.", "evidenceNotes": [ "Strong evidence for the classic endocrine indications; thin evidence for the popular modern one." ], "tags": [ "testosterone", "fertility", "TRT", "GnRH", "compounded" ], "confusedWith": [ { "slug": "leuprolide", "why": "The single most consequential confusion in this category. Both target the GnRH receptor. Pulsatile gonadorelin stimulates the axis; continuous leuprolide suppresses it to castrate levels. Dosing frequency reverses the effect." }, { "slug": "hcg", "why": "Both used to preserve testicular function on testosterone therapy, but at different levels. hCG acts directly on the LH receptor in the testis; gonadorelin acts upstream at the pituitary and needs an intact pituitary to work." } ] }, { "slug": "hexarelin", "name": "Hexarelin", "aka": [ "Examorelin" ], "category": "growth", "chemClass": "Synthetic hexapeptide GH secretagogue", "route": "Subcutaneous or intravenous (research)", "halfLife": "~55 minutes", "status": "research", "statusNote": "Not approved. Studied in cardiac research; abandoned for therapeutic development.", "evidence": 2, "summary": "The most potent GH releaser of the classical GHRP family, and the one that desensitises fastest. Its more interesting biology may be cardiac rather than pituitary — it binds CD36 in heart tissue independently of GH.", "mechanism": "Ghrelin receptor agonism producing a large GH pulse, plus binding to the CD36 scavenger receptor in cardiac and vascular tissue, which mediates GH-independent cardioprotective effects in animal models.", "studied": "Acute GH-release pharmacology in humans; preclinical cardiac ischemia models; small human cardiac studies.", "benefits": [ { "t": "Highest GH release potency in class", "d": "Produces larger acute GH pulses than GHRP-2 or GHRP-6.", "s": "moderate" }, { "t": "GH-independent cardioprotection signals", "d": "Preclinical models show improved cardiac function after ischemia via CD36, independent of GH.", "s": "preliminary" }, { "t": "Retains some activity in GH-deficient states", "d": "The cardiac effects do not require an intact GH axis.", "s": "preliminary" } ], "risks": [ { "t": "Rapid and marked tachyphylaxis", "d": "GH response falls substantially within about two weeks of continuous use — arguably the defining practical problem.", "s": "moderate" }, { "t": "Cortisol and prolactin elevation", "d": "Significant; more than GHRP-2.", "s": "moderate" }, { "t": "No approved indication", "d": "Development was not completed for any use.", "s": "high" }, { "t": "Cardiac effects unstudied in chronic human use", "d": "The CD36 biology is interesting but entirely uncharacterised long-term in people.", "s": "high" }, { "t": "Unregulated supply", "d": "Research-chemical market.", "s": "high" }, { "t": "WADA prohibited", "d": "Banned in sport.", "s": "low" } ], "avoid": [ "Active malignancy", "Pregnancy", "Cardiac disease outside a research setting", "Hyperprolactinemia" ], "monitoring": [ "IGF-1, prolactin, cortisol", "Glucose" ], "legal": "Not approved for human use.", "evidenceNotes": [ "Acute human pharmacology well described; no chronic efficacy or safety data." ], "tags": [ "growth hormone", "ghrelin", "cardiac", "research chemical" ] }, { "slug": "hcg", "name": "Human Chorionic Gonadotropin (hCG)", "aka": [ "Pregnyl", "Novarel", "Ovidrel" ], "category": "hormonal", "chemClass": "Glycoprotein hormone with an LH-like beta subunit — technically a glycoprotein rather than a simple peptide", "route": "Intramuscular or subcutaneous", "halfLife": "~24–36 hours", "status": "approved", "statusNote": "FDA-approved for hypogonadotropic hypogonadism, prepubertal cryptorchidism, and ovulation induction. FDA prohibited OTC hCG weight-loss products in 2011.", "evidence": 5, "summary": "A long-approved hormone with well-defined indications and one of the most thoroughly debunked claims in diet history. The legitimate uses are real; the weight-loss protocol is not.", "mechanism": "Binds and activates the LH receptor, stimulating Leydig cell testosterone production in men and triggering ovulation in women. Its long half-life relative to LH makes it useful clinically.", "studied": "Decades of trials in fertility, hypogonadism and cryptorchidism; multiple randomized trials specifically testing and refuting the hCG diet.", "benefits": [ { "t": "Restores testicular testosterone production", "d": "Established efficacy in hypogonadotropic hypogonadism and in preserving testicular function during exogenous testosterone therapy.", "s": "strong" }, { "t": "Preserves fertility on TRT", "d": "Maintains intratesticular testosterone and spermatogenesis where testosterone alone would suppress both.", "s": "strong" }, { "t": "Ovulation induction", "d": "Standard trigger in assisted reproduction protocols.", "s": "strong" }, { "t": "Cryptorchidism treatment", "d": "Approved use in prepubertal boys with undescended testes.", "s": "strong" } ], "risks": [ { "t": "The hCG diet does not work", "d": "Randomized trials repeatedly found no weight loss or appetite benefit beyond the accompanying 500-calorie diet — which is itself the actual and dangerous intervention.", "s": "high" }, { "t": "Ovarian hyperstimulation syndrome", "d": "A potentially life-threatening complication of ovulation induction requiring specialist monitoring.", "s": "high" }, { "t": "Estradiol elevation and gynecomastia in men", "d": "Increased testosterone production raises aromatisation; gynecomastia is a common consequence.", "s": "moderate" }, { "t": "Thromboembolism risk", "d": "Reported particularly in the context of ovarian hyperstimulation.", "s": "high" }, { "t": "Multiple pregnancy", "d": "A recognised consequence of ovulation induction.", "s": "moderate" }, { "t": "Precocious puberty in boys", "d": "Risk when used in prepubertal patients without endocrinology supervision.", "s": "moderate" } ], "avoid": [ "Hormone-sensitive cancers including prostate cancer", "Precocious puberty", "Unexplained uterine bleeding", "Weight-loss use of any kind" ], "monitoring": [ "Testosterone and estradiol in men", "Ultrasound and estradiol during ovulation induction", "Hematocrit" ], "legal": "Prescription drug. OTC and homeopathic hCG weight-loss products are unlawful in the US.", "evidenceNotes": [ "A useful example of strong evidence both for legitimate uses and against a popular misuse." ], "tags": [ "fertility", "testosterone", "TRT", "debunked diet", "approved" ], "interactions": [ "Exogenous testosterone — suppresses the axis hCG is being used to preserve; timing and dosing matter", "Aromatase inhibitors — often co-prescribed to control the estradiol rise from increased testosterone production", "Gonadotropin preparations — additive ovarian hyperstimulation risk" ] }, { "slug": "humanin", "name": "Humanin", "aka": [ "HN", "HNG (potent analog)" ], "category": "longevity", "chemClass": "Mitochondrial-derived peptide — 24 amino acids", "route": "Subcutaneous or intracerebroventricular (research)", "halfLife": "Short; analogs engineered for longer duration", "status": "research", "statusNote": "Not approved. Preclinical neuroprotection and metabolic research compound.", "evidence": 1, "summary": "Discovered in surviving neurons of Alzheimer brains, which is a striking origin story. It is cytoprotective in a wide range of stress models, and plasma levels decline with age. None of that has yet been tested as a treatment in humans.", "mechanism": "Binds a trimeric receptor complex and interacts with pro-apoptotic Bcl-2 family proteins, inhibiting Bax-mediated apoptosis. Also activates STAT3 signalling and improves insulin sensitivity in animal models.", "studied": "Rodent models of Alzheimer disease, stroke, myocardial infarction, and metabolic disease; human observational studies of circulating levels versus age and disease.", "benefits": [ { "t": "Neuroprotection in animal models", "d": "Protects neurons against amyloid-beta toxicity and ischemic injury across multiple rodent models.", "s": "preliminary" }, { "t": "Anti-apoptotic activity", "d": "A well-characterised molecular mechanism inhibiting Bax-mediated cell death.", "s": "preliminary" }, { "t": "Metabolic effects", "d": "Improves insulin sensitivity and reduces visceral fat in rodents.", "s": "preliminary" }, { "t": "Declines with age in humans", "d": "Circulating levels fall with age and are higher in offspring of centenarians — an interesting association.", "s": "preliminary" } ], "risks": [ { "t": "No human trials", "d": "No interventional human data exists.", "s": "high" }, { "t": "Anti-apoptotic effects are double-edged", "d": "Blocking programmed cell death systemically is exactly the mechanism by which damaged and pre-cancerous cells survive.", "s": "high" }, { "t": "Poor pharmacokinetics", "d": "Rapid clearance and questionable CNS penetration for the native peptide.", "s": "moderate" }, { "t": "Unregulated supply", "d": "Research-chemical market.", "s": "high" } ], "avoid": [ "Human use outside research settings", "Any cancer history" ], "monitoring": [ "No validated monitoring exists" ], "legal": "Not approved for human use.", "evidenceNotes": [ "Active academic research area; no clinical translation to date." ], "tags": [ "mitochondria", "neuroprotection", "apoptosis", "longevity", "preclinical only" ] }, { "slug": "igf-1-lr3", "name": "IGF-1 LR3", "aka": [ "Long R3 IGF-1" ], "category": "growth", "chemClass": "Modified insulin-like growth factor 1 analog with reduced binding-protein affinity", "route": "Subcutaneous (research reagent)", "halfLife": "~20–30 hours (versus ~10 minutes for native free IGF-1)", "status": "research", "statusNote": "Sold as a cell-culture research reagent. Never developed for human therapeutic use. WADA-prohibited.", "evidence": 1, "summary": "A laboratory reagent engineered to evade IGF-binding proteins so it stays active in cell culture. Applying that design to a human body removes the buffering system that normally keeps IGF-1 signalling controlled — which is exactly the point of concern.", "mechanism": "Binds the IGF-1 receptor, driving PI3K/Akt and MAPK signalling: protein synthesis, satellite-cell activation, cell proliferation and survival. The R3 substitution and 13-residue N-terminal extension drastically reduce IGFBP binding, producing sustained unbuffered receptor activation.", "studied": "Cell culture and animal research only. No human clinical trials of the LR3 analog exist.", "benefits": [ { "t": "Potent anabolic signalling in vitro", "d": "Reliably drives protein synthesis and cell proliferation in laboratory models — this is its intended purpose.", "s": "preliminary" }, { "t": "Native IGF-1 has approved uses", "d": "Recombinant human IGF-1 (mecasermin) is approved for severe primary IGF-1 deficiency, establishing that the pathway is therapeutically tractable. LR3 is not that drug.", "s": "moderate" } ], "risks": [ { "t": "Hypoglycemia", "d": "IGF-1 has meaningful insulin-receptor cross-reactivity; severe hypoglycemia is the most common acute harm reported with IGF-1 analogs.", "s": "high" }, { "t": "Cancer promotion concern", "d": "Elevated IGF-1 signalling is epidemiologically associated with several cancers and is a core proliferative pathway. Unbuffered chronic elevation is the worst-case version of this exposure.", "s": "high" }, { "t": "No human safety data whatsoever", "d": "There is no dose that has been shown to be safe in people, because none has been studied.", "s": "high" }, { "t": "Organ and tissue overgrowth", "d": "Animal models show visceral organ growth with sustained IGF-1 elevation.", "s": "moderate" }, { "t": "Reagent-grade manufacturing", "d": "Products are labelled and manufactured for laboratory use, not for injection into humans.", "s": "high" }, { "t": "WADA prohibited", "d": "Banned at all times.", "s": "low" } ], "avoid": [ "All human use — this is a laboratory reagent, not a medicine" ], "monitoring": [ "Not applicable" ], "legal": "Not approved for human use anywhere. Sold under research-use-only labelling.", "evidenceNotes": [ "Zero human clinical trials. Everything known comes from cell culture and animals." ], "tags": [ "IGF-1", "anabolic", "research reagent", "high risk" ], "interactions": [ "Insulin — additive and potentially severe hypoglycemia", "Growth hormone and secretagogues — compound IGF-1 elevation", "Corticosteroids — oppose the anabolic effect" ] }, { "slug": "ipamorelin", "name": "Ipamorelin", "aka": [ "NNC 26-0161" ], "category": "growth", "chemClass": "Selective ghrelin receptor (GHS-R1a) agonist — pentapeptide", "route": "Subcutaneous (research)", "halfLife": "~2 hours", "status": "research", "statusNote": "Investigational; phase 2 trials in postoperative ileus were discontinued. Not approved. Common in compounded wellness protocols.", "evidence": 2, "summary": "The most selective of the growth hormone-releasing peptides — it triggers GH release with minimal effect on cortisol, prolactin or appetite. That selectivity is real and is why it displaced GHRP-6 in clinical practice. Efficacy for the outcomes people actually want it for is not established.", "mechanism": "Agonises the ghrelin receptor on pituitary somatotrophs, amplifying GH pulse amplitude and suppressing somatostatin tone. Unlike earlier GHRPs it has little affinity for the pathways that drive ACTH/cortisol and prolactin release.", "studied": "Phase 2 trials for postoperative ileus (development stopped); animal studies on bone and GH secretion.", "benefits": [ { "t": "Selective GH release", "d": "Clean pharmacology: GH rises without the cortisol and prolactin spikes seen with hexarelin or GHRP-6.", "s": "moderate" }, { "t": "Minimal appetite stimulation", "d": "Unlike GHRP-6, it does not produce the intense hunger that makes those peptides impractical.", "s": "moderate" }, { "t": "Good short-term tolerability", "d": "Trial safety data in the ileus program were reassuring over short exposures.", "s": "moderate" }, { "t": "Synergy with GHRH analogs", "d": "The two mechanisms combine to produce a larger pulse than either alone.", "s": "moderate" } ], "risks": [ { "t": "No proven clinical benefit", "d": "The trials that were run targeted gut motility and were discontinued. Body-composition and recovery claims are untested.", "s": "high" }, { "t": "Unapproved and unregulated", "d": "Available only through compounding or grey-market suppliers, with corresponding quality uncertainty.", "s": "high" }, { "t": "Glucose and insulin effects", "d": "Raising the GH axis can worsen insulin sensitivity over time.", "s": "moderate" }, { "t": "Receptor desensitisation", "d": "Continuous ghrelin-receptor stimulation blunts the response; effects diminish with sustained use.", "s": "moderate" }, { "t": "Head/injection-site reactions", "d": "Headache, flushing and local reactions are reported.", "s": "low" }, { "t": "Prohibited in sport", "d": "WADA-banned.", "s": "low" } ], "avoid": [ "Active malignancy", "Pregnancy", "Poorly controlled diabetes" ], "monitoring": [ "IGF-1", "Fasting glucose", "Cortisol only if symptomatic" ], "legal": "Not FDA-approved. FDA placed several GH-secretagogue peptides under increased compounding scrutiny.", "evidenceNotes": [ "Human data limited to discontinued phase 2 work in an unrelated indication." ], "tags": [ "growth hormone", "ghrelin", "GHRP", "compounded" ], "confusedWith": [ { "slug": "ghrp-2", "why": "Both ghrelin receptor agonists. Ipamorelin is selective and spares cortisol and prolactin; GHRP-2 is more potent at releasing GH but raises both." }, { "slug": "mk-677", "why": "Same receptor, but MK-677 is an oral non-peptide with sustained rather than pulsatile action — and the only one of the two with a long-term human trial, which found a heart failure signal." } ] }, { "slug": "kisspeptin-10", "name": "Kisspeptin-10", "aka": [ "KP-10", "metastin fragment" ], "category": "hormonal", "chemClass": "Decapeptide fragment of kisspeptin, the master regulator of GnRH release", "route": "Intravenous or subcutaneous (research)", "halfLife": "Very short — minutes", "status": "trials", "statusNote": "Investigational. Studied in academic reproductive endocrinology trials, notably at Imperial College London. Not approved.", "evidence": 3, "summary": "The upstream switch for the entire reproductive hormone axis. Serious academic trials have examined it for fertility treatment and for sexual desire disorders in both sexes, which is more than most peptides here can claim.", "mechanism": "Binds KISS1R (GPR54) on hypothalamic GnRH neurons, triggering GnRH release and downstream LH and FSH secretion. Also has direct effects on limbic brain regions processing sexual and emotional stimuli, independent of the hormonal cascade.", "studied": "Trials as a trigger for oocyte maturation in IVF (reducing ovarian hyperstimulation risk), and randomized crossover trials in men and women with hypoactive sexual desire disorder.", "benefits": [ { "t": "Safer IVF trigger", "d": "Studied as an alternative to hCG for triggering oocyte maturation, with a lower risk of ovarian hyperstimulation syndrome — a genuinely dangerous complication.", "s": "moderate" }, { "t": "Sexual desire effects in randomized trials", "d": "Crossover trials in men and women with HSDD showed enhanced limbic responses to sexual stimuli and improved sexual response measures.", "s": "moderate" }, { "t": "Physiological upstream mechanism", "d": "Acts at the top of the reproductive axis, preserving downstream pulsatility and feedback.", "s": "moderate" }, { "t": "Good short-term tolerability", "d": "Academic trials reported minimal adverse effects with acute dosing.", "s": "moderate" } ], "risks": [ { "t": "Not approved", "d": "No regulatory authorisation for any indication.", "s": "high" }, { "t": "Very short half-life", "d": "Requires infusion or frequent dosing; practical delivery remains a barrier.", "s": "moderate" }, { "t": "Receptor desensitisation with continuous exposure", "d": "Sustained stimulation suppresses rather than stimulates the axis — the same paradox seen with GnRH agonists.", "s": "moderate" }, { "t": "Reproductive axis manipulation", "d": "Effects on menstrual cycles, fertility and hormone balance with chronic non-supervised use are unstudied.", "s": "high" }, { "t": "Grey-market sale", "d": "Sold as a research peptide for libido, well outside the trial contexts that generated the data.", "s": "high" } ], "avoid": [ "Hormone-sensitive cancers", "Pregnancy", "Unsupervised use for libido" ], "monitoring": [ "LH, FSH, sex hormones if used clinically", "Menstrual cycle tracking" ], "legal": "Investigational only.", "evidenceNotes": [ "Real academic randomized trials, but early-phase and in narrow contexts." ], "tags": [ "fertility", "libido", "reproductive", "GnRH", "investigational" ] }, { "slug": "kpv", "name": "KPV", "aka": [ "Lysine-Proline-Valine", "α-MSH (11-13)" ], "category": "immune", "chemClass": "C-terminal tripeptide fragment of alpha-melanocyte-stimulating hormone", "route": "Oral, topical, or subcutaneous (research)", "halfLife": "Short; not well characterised", "status": "research", "statusNote": "Not approved. Preclinical anti-inflammatory research compound; increasingly marketed for gut and skin inflammation.", "evidence": 1, "summary": "The smallest active piece of alpha-MSH, retaining the anti-inflammatory activity while dropping the pigmentation effects. The preclinical inflammatory bowel data is genuinely interesting. Human data does not exist.", "mechanism": "Enters cells and inhibits NF-κB nuclear translocation and downstream pro-inflammatory cytokine production (TNF-α, IL-6, IL-1β), apparently without requiring melanocortin receptor binding. Also shows direct antimicrobial activity against some organisms in vitro.", "studied": "Rodent colitis models, in-vitro immune cell work, and topical dermatology models. No completed human trials.", "benefits": [ { "t": "Anti-inflammatory without pigmentation", "d": "Retains alpha-MSH anti-inflammatory activity while lacking the melanocortin pigmentation effect — a clean pharmacological separation.", "s": "preliminary" }, { "t": "Colitis improvement in rodents", "d": "Oral and rectal delivery reduce colonic inflammation in animal models of inflammatory bowel disease.", "s": "preliminary" }, { "t": "Antimicrobial activity in vitro", "d": "Activity against Candida and some bacteria in laboratory models.", "s": "preliminary" }, { "t": "Favourable preclinical safety", "d": "Small tripeptides with endogenous origins generally show low toxicity in animal work.", "s": "preliminary" } ], "risks": [ { "t": "No human trials", "d": "All efficacy claims are preclinical extrapolation.", "s": "high" }, { "t": "Immune modulation is not inherently benign", "d": "Suppressing NF-κB signalling long-term has implications for infection surveillance and tumour immunity that have not been studied.", "s": "moderate" }, { "t": "Unapproved and unregulated", "d": "Research-chemical supply chain.", "s": "high" }, { "t": "Delivery and stability poorly characterised", "d": "How much survives oral administration in humans is unknown.", "s": "moderate" } ], "avoid": [ "Immunosuppressed patients", "Pregnancy", "Active infection" ], "monitoring": [ "No validated monitoring exists" ], "legal": "Not approved for human use.", "evidenceNotes": [ "Promising preclinical anti-inflammatory data; the human translation step has not been attempted." ], "tags": [ "inflammation", "gut health", "skin", "research chemical" ] }, { "slug": "larazotide", "name": "Larazotide Acetate", "aka": [ "AT-1001", "INN-202" ], "category": "gut", "chemClass": "Octapeptide tight-junction regulator (zonulin antagonist)", "route": "Oral", "halfLife": "Minimal systemic absorption — acts locally in the gut lumen", "status": "trials", "statusNote": "Reached phase 3 for celiac disease; the trial did not meet its primary endpoint and was discontinued in 2022. Not approved.", "evidence": 3, "summary": "The furthest any \"leaky gut\" therapy has progressed through formal drug development — all the way to phase 3, where it failed. That result is important context for the intestinal-permeability claims made across the supplement industry.", "mechanism": "Antagonises zonulin signalling to tighten intestinal epithelial tight junctions, reducing paracellular passage of gliadin peptides. It is designed to act locally in the gut lumen with negligible systemic absorption.", "studied": "Multiple phase 2 trials in celiac disease showing symptom benefit; the CeDLara phase 3 trial, stopped for futility at interim analysis.", "benefits": [ { "t": "Phase 2 symptom improvement in celiac disease", "d": "Earlier randomized trials showed reduced gastrointestinal symptoms in patients on a gluten-free diet with persistent symptoms.", "s": "moderate" }, { "t": "Excellent safety profile", "d": "Negligible systemic absorption; adverse events comparable to placebo across a large trial program.", "s": "strong" }, { "t": "Validated a mechanism", "d": "Demonstrated that tight-junction modulation is pharmacologically achievable, even if the clinical payoff was not delivered.", "s": "moderate" } ], "risks": [ { "t": "Failed phase 3", "d": "The definitive trial stopped for futility. This is the most important thing to know about it.", "s": "high" }, { "t": "Not available", "d": "No approved product; no lawful supply.", "s": "moderate" }, { "t": "Headache and gastrointestinal symptoms", "d": "The most commonly reported events, generally mild.", "s": "low" } ], "avoid": [ "Not applicable — no lawful supply exists" ], "monitoring": [ "Not applicable" ], "legal": "Investigational; development discontinued.", "evidenceNotes": [ "A well-run program with a negative definitive result — genuinely useful evidence." ], "tags": [ "gut health", "celiac", "failed phase 3", "tight junction" ], "confusedWith": [ { "slug": "bpc-157", "why": "Both marketed for \"leaky gut\". Larazotide is the only tight-junction drug to reach phase 3 — where it failed. BPC-157 has never had a published randomized human trial at all." } ] }, { "slug": "leuprolide", "name": "Leuprolide", "aka": [ "Lupron", "Eligard", "leuprorelin" ], "category": "hormonal", "chemClass": "GnRH receptor superagonist — nonapeptide analog of gonadotropin-releasing hormone", "route": "Subcutaneous or intramuscular depot (monthly to 6-monthly)", "halfLife": "~3 hours (depot formulations release over months)", "status": "approved", "statusNote": "FDA-approved for advanced prostate cancer, endometriosis, uterine fibroids and central precocious puberty.", "evidence": 5, "summary": "The definitive demonstration that dosing pattern determines direction. Leuprolide is a more potent GnRH agonist than the natural hormone — and because it is given continuously rather than in pulses, it shuts the reproductive axis down instead of switching it on.", "mechanism": "Continuous GnRH receptor occupancy causes receptor downregulation and pituitary desensitisation after an initial surge. LH and FSH fall, and gonadal steroid production drops to castrate levels within 2–4 weeks. Pulsatile GnRH, by contrast, stimulates the axis — which is why gonadorelin and leuprolide have opposite clinical effects.", "studied": "Decades of randomized trials in prostate cancer, endometriosis, uterine fibroids and central precocious puberty.", "benefits": [ { "t": "Effective androgen deprivation in prostate cancer", "d": "Achieves castrate testosterone levels reliably, a cornerstone of advanced prostate cancer treatment.", "s": "strong" }, { "t": "Halts central precocious puberty", "d": "Arrests premature pubertal progression and preserves adult height potential, with the effect reversing on discontinuation.", "s": "strong" }, { "t": "Reduces endometriosis pain and fibroid volume", "d": "Randomized evidence in both indications.", "s": "strong" }, { "t": "Long-acting depot formulations", "d": "Dosing intervals from one to six months substantially improve adherence.", "s": "strong" } ], "risks": [ { "t": "Testosterone flare in the first two weeks", "d": "The initial agonist surge can worsen prostate cancer symptoms, causing spinal cord compression or urinary obstruction. Anti-androgen cover is required in patients at risk.", "s": "high" }, { "t": "Bone mineral density loss", "d": "Sustained hypogonadism causes progressive bone loss and osteoporotic fracture risk with long-term use.", "s": "high" }, { "t": "Cardiometabolic effects", "d": "Androgen deprivation is associated with insulin resistance, dyslipidaemia and increased cardiovascular risk.", "s": "high" }, { "t": "Vasomotor and sexual side effects", "d": "Hot flushes, loss of libido and erectile dysfunction are near-universal in men.", "s": "moderate" }, { "t": "Mood effects", "d": "Depression and emotional lability are commonly reported, and specifically flagged in pediatric use.", "s": "moderate" }, { "t": "Fetal harm", "d": "Contraindicated in pregnancy.", "s": "high" }, { "t": "Add-back therapy usually required", "d": "For endometriosis and fibroids, hormonal add-back is standard to limit bone loss, which complicates the regimen.", "s": "moderate" } ], "avoid": [ "Pregnancy and breastfeeding", "Undiagnosed abnormal vaginal bleeding", "Known hypersensitivity to GnRH analogs", "Caution with pre-existing osteoporosis" ], "monitoring": [ "Testosterone and PSA in prostate cancer", "Bone mineral density with therapy beyond 6 months", "Glucose, HbA1c and lipids", "Growth velocity and bone age in pediatric use", "Mood assessment" ], "legal": "Prescription drug.", "evidenceNotes": [ "Decades of randomized trials across four distinct approved indications." ], "interactions": [ "Drugs that prolong QT — androgen deprivation adds risk", "Antihyperglycemic agents — requirements often increase" ], "confusedWith": [ { "slug": "gonadorelin", "why": "Same receptor, opposite outcome. Gonadorelin given in pulses stimulates the axis and is used to preserve testicular function. Leuprolide given continuously suppresses it to castrate levels. The dosing pattern, not the molecule, decides the direction." } ], "tags": [ "prostate cancer", "endometriosis", "GnRH", "precocious puberty", "approved" ] }, { "slug": "linaclotide", "name": "Linaclotide", "aka": [ "Linzess", "Constella" ], "category": "gut", "chemClass": "Guanylate cyclase-C agonist — 14-amino-acid peptide with three disulfide bridges", "route": "Oral capsule, once daily", "halfLife": "Minimally absorbed — acts locally in the gut lumen", "status": "approved", "statusNote": "FDA-approved for irritable bowel syndrome with constipation and for chronic idiopathic constipation, including a pediatric indication.", "evidence": 5, "summary": "Proof that an oral peptide drug can work well — by not being absorbed at all. Linaclotide acts entirely on the luminal surface of the gut and is essentially undetectable in blood, which sidesteps the systemic side effects that limit most peptides.", "mechanism": "Agonises guanylate cyclase-C on the luminal surface of intestinal epithelium, raising intracellular and extracellular cyclic GMP. That increases chloride and bicarbonate secretion, drawing fluid into the lumen and accelerating transit. Extracellular cGMP also reduces visceral afferent nociceptor firing, which explains the pain benefit that laxatives do not provide.", "studied": "Multiple phase 3 trials in IBS-C and chronic idiopathic constipation; a dedicated pediatric functional constipation program.", "benefits": [ { "t": "Relieves both constipation and abdominal pain", "d": "The visceral analgesic effect is mechanistically distinct from the laxative effect, and is what separates it from osmotic laxatives.", "s": "strong" }, { "t": "Essentially no systemic exposure", "d": "Plasma concentrations are generally below the limit of quantification, which largely removes systemic drug interactions.", "s": "strong" }, { "t": "Consistent phase 3 results", "d": "Replicated across multiple trials in both indications with validated symptom endpoints.", "s": "strong" }, { "t": "Pediatric indication", "d": "Approved for functional constipation in children within a defined age range, supported by its own trial.", "s": "strong" } ], "risks": [ { "t": "Boxed warning: contraindicated in young children", "d": "Contraindicated under 2 years of age due to fatal dehydration in juvenile animal studies. This is an absolute contraindication, not a caution.", "s": "high" }, { "t": "Diarrhea", "d": "The most common adverse effect and the main reason for discontinuation — an on-target consequence of the mechanism.", "s": "moderate" }, { "t": "Severe diarrhea and dehydration", "d": "Can be serious in the elderly or in anyone unable to maintain fluid intake; the drug should be stopped.", "s": "high" }, { "t": "Contraindicated in mechanical obstruction", "d": "Increasing intestinal secretion behind an obstruction is dangerous.", "s": "high" }, { "t": "Abdominal pain, bloating and flatulence", "d": "Common early in treatment.", "s": "low" } ], "avoid": [ "Children under 2 years — boxed warning", "Known or suspected mechanical gastrointestinal obstruction", "Severe dehydration" ], "monitoring": [ "Stool frequency and consistency", "Hydration status, particularly in elderly patients", "Symptom response at 4–12 weeks" ], "legal": "Prescription drug.", "evidenceNotes": [ "Multiple replicated phase 3 trials with patient-reported endpoints agreed with regulators in advance." ], "interactions": [ "Minimal — negligible systemic absorption means essentially no pharmacokinetic drug interactions", "Other laxatives — additive diarrhea risk" ], "confusedWith": [ { "slug": "plecanatide", "why": "Same target and same indications. Plecanatide is modelled on uroguanylin and is pH-sensitive, which is claimed to concentrate activity in the small intestine and reduce diarrhea rates." } ], "tags": [ "IBS", "constipation", "oral peptide", "approved", "gut" ] }, { "slug": "liraglutide", "name": "Liraglutide", "aka": [ "Victoza", "Saxenda" ], "category": "metabolic", "chemClass": "GLP-1 receptor agonist — acylated GLP-1 analog", "route": "Subcutaneous, once daily", "halfLife": "~13 hours", "status": "approved", "statusNote": "FDA-approved for type 2 diabetes (2010) and chronic weight management (2014); generic versions now available", "evidence": 5, "summary": "The first-generation weekly-to-daily GLP-1. Superseded on efficacy by semaglutide and tirzepatide, but it has the longest real-world safety record, daily dosing that is easier to stop quickly, and is now the cheapest option in the class.", "mechanism": "Same GLP-1 receptor pharmacology as semaglutide with a shorter C16 fatty-acid chain, giving a daily rather than weekly dosing interval.", "studied": "LEAD program (diabetes), SCALE program (obesity), LEADER (cardiovascular outcomes).", "benefits": [ { "t": "Proven cardiovascular benefit", "d": "The LEADER trial demonstrated reduced major adverse cardiovascular events in type 2 diabetes with high cardiovascular risk.", "s": "strong" }, { "t": "Moderate weight loss", "d": "Around 8% mean body-weight reduction at 3.0 mg daily in SCALE — less than newer agents but clinically meaningful.", "s": "strong" }, { "t": "Approved in adolescents", "d": "Has pediatric obesity and pediatric type 2 diabetes indications, giving it a role newer drugs took longer to earn.", "s": "strong" }, { "t": "Rapid washout", "d": "The short half-life means side effects resolve within days of stopping, useful in fragile or elderly patients.", "s": "moderate" }, { "t": "Now available as a generic", "d": "Cost has fallen sharply, making it the most accessible lawful GLP-1 in many markets.", "s": "strong" } ], "risks": [ { "t": "Daily injection burden", "d": "Adherence is measurably worse than with weekly agents.", "s": "low" }, { "t": "GI intolerance", "d": "Nausea and vomiting, particularly during titration.", "s": "moderate" }, { "t": "Thyroid C-cell boxed warning", "d": "Same class contraindication for medullary thyroid carcinoma and MEN2.", "s": "high" }, { "t": "Pancreatitis and gallbladder disease", "d": "Class effects, uncommon but serious.", "s": "high" }, { "t": "Lower efficacy than newer agents", "d": "If maximal weight loss is the goal, liraglutide is a compromise choice.", "s": "low" } ], "avoid": [ "Medullary thyroid carcinoma or MEN2 history", "Pregnancy", "Prior pancreatitis (relative)" ], "monitoring": [ "HbA1c, weight", "Renal function during GI illness" ], "legal": "Prescription drug, now including generic formulations.", "evidenceNotes": [ "Over a decade of post-marketing surveillance.", "Dedicated cardiovascular outcome trial with positive result." ], "tags": [ "weight loss", "diabetes", "GLP-1", "generic" ], "interactions": [ "Insulin and sulfonylureas — hypoglycemia risk; dose reduction usually needed", "Oral medications — delayed gastric emptying affects absorption", "Warfarin — monitor INR" ] }, { "slug": "ll-37", "name": "LL-37", "aka": [ "Cathelicidin", "hCAP-18 fragment" ], "category": "antimicrobial", "chemClass": "Human cathelicidin antimicrobial peptide — 37 residues", "route": "Topical or subcutaneous (research)", "halfLife": "Short; rapidly degraded", "status": "research", "statusNote": "Not approved. Studied topically for chronic wounds; systemic use unstudied. Has a genuine pro-inflammatory disease association.", "evidence": 2, "summary": "The body's own broad-spectrum antimicrobial peptide, and a good illustration of why \"natural\" does not mean \"safe to add more of\". LL-37 is also directly implicated in the pathology of psoriasis, rosacea and lupus.", "mechanism": "Amphipathic helical peptide that disrupts bacterial membranes and neutralises endotoxin. It also acts as an immune signalling molecule, chemoattracting neutrophils and monocytes, and — critically — forms complexes with self-DNA and RNA that activate plasmacytoid dendritic cells, driving interferon responses.", "studied": "Small phase 1/2 topical trials in hard-to-heal venous leg ulcers; extensive immunology research; substantial literature on its role in autoimmune skin disease.", "benefits": [ { "t": "Broad-spectrum antimicrobial activity", "d": "Active against bacteria, fungi and some viruses, including biofilm-forming organisms, with a membrane mechanism that resists conventional resistance development.", "s": "moderate" }, { "t": "Chronic wound healing signal", "d": "A small randomized topical trial in venous leg ulcers showed improved healing rates.", "s": "preliminary" }, { "t": "Endotoxin neutralisation", "d": "Binds and neutralises bacterial LPS in laboratory models.", "s": "preliminary" }, { "t": "Immune cell recruitment", "d": "Chemotactic for neutrophils, monocytes and T cells.", "s": "preliminary" } ], "risks": [ { "t": "Drives autoimmune skin disease", "d": "LL-37 is overexpressed in psoriasis and rosacea lesions and functions as an autoantigen in psoriasis. Adding more is mechanistically the wrong direction in these conditions.", "s": "high" }, { "t": "Pro-inflammatory at higher concentrations", "d": "The same peptide is antimicrobial at low concentration and inflammatory at high concentration — a narrow therapeutic window.", "s": "high" }, { "t": "Cytotoxic to human cells at higher doses", "d": "Membrane-disrupting activity is not perfectly selective for microbes.", "s": "moderate" }, { "t": "No systemic human data", "d": "Injectable use has never been evaluated.", "s": "high" }, { "t": "Lupus association", "d": "LL-37-DNA complexes are implicated in systemic lupus erythematosus pathogenesis.", "s": "high" } ], "avoid": [ "Psoriasis, rosacea, or lupus", "Any autoimmune inflammatory condition", "Pregnancy", "Systemic use generally" ], "monitoring": [ "No validated monitoring exists" ], "legal": "Not approved for human use.", "evidenceNotes": [ "One of the clearest examples of a peptide whose known biology argues against casual use." ], "tags": [ "antimicrobial", "wound healing", "inflammation", "high risk" ], "confusedWith": [ { "slug": "kpv", "why": "Both host-derived peptides sold for inflammation, with opposite immune directions. KPV suppresses NF-kB signalling; LL-37 is pro-inflammatory at higher concentrations and drives psoriasis and lupus pathology." } ] }, { "slug": "macimorelin", "name": "Macimorelin", "aka": [ "Macrilen", "AEZS-130" ], "category": "growth", "chemClass": "Orally active ghrelin receptor agonist — peptidomimetic", "route": "Oral, single diagnostic dose", "halfLife": "~4 hours", "status": "approved", "statusNote": "FDA-approved (2017) and EMA-approved for the diagnosis of adult growth hormone deficiency.", "evidence": 5, "summary": "The only orally administered growth hormone secretagogue with full FDA approval — and it is approved as a diagnostic test, taken once, not as a therapy. That distinction is the whole point of including it.", "mechanism": "Ghrelin receptor agonism producing a reliable, reproducible growth hormone pulse. Its diagnostic value rests on that reproducibility: a peak GH below a defined threshold after a single oral dose confirms adult GH deficiency.", "studied": "Pivotal randomized crossover trial against the insulin tolerance test, the previous reference standard.", "benefits": [ { "t": "Replaces a genuinely dangerous test", "d": "The insulin tolerance test requires deliberately inducing hypoglycemia under supervision and is contraindicated in cardiac disease and epilepsy. Macimorelin achieves comparable diagnostic accuracy with an oral solution.", "s": "strong" }, { "t": "High diagnostic agreement", "d": "The pivotal trial showed sensitivity and specificity closely matching the insulin tolerance test.", "s": "strong" }, { "t": "Oral and outpatient", "d": "No infusion, no induced hypoglycemia, no intensive monitoring.", "s": "strong" }, { "t": "Proves oral GH secretagogues are feasible", "d": "A useful reference point when assessing unapproved oral secretagogue claims.", "s": "moderate" } ], "risks": [ { "t": "Diagnostic use only", "d": "It is not a treatment. There is no evidence base for repeated dosing, and no approval for therapeutic use.", "s": "high" }, { "t": "QT interval prolongation", "d": "The main safety concern; concurrent QT-prolonging drugs must be stopped before testing.", "s": "high" }, { "t": "Dysgeusia", "d": "A distorted or metallic taste is the most common adverse effect.", "s": "low" }, { "t": "False results with interfering drugs", "d": "Strong CYP3A4 inducers and recent GH therapy can invalidate the test.", "s": "moderate" }, { "t": "Fatigue and headache", "d": "Reported after the single dose.", "s": "low" } ], "avoid": [ "Concurrent QT-prolonging medication", "Known congenital long QT syndrome", "Use as a therapy rather than a diagnostic" ], "monitoring": [ "ECG before testing where QT risk exists", "Serial GH sampling per the test protocol", "Review of interfering medications" ], "legal": "Prescription diagnostic agent, administered under medical supervision.", "evidenceNotes": [ "Head-to-head validation against the previous reference standard — the right trial design for a diagnostic." ], "interactions": [ "QT-prolonging drugs — must be discontinued before testing", "Strong CYP3A4 inducers — can cause false results", "Recent growth hormone therapy — invalidates the test" ], "confusedWith": [ { "slug": "mk-677", "why": "Both are orally active ghrelin receptor agonists. Macimorelin is FDA-approved for a single diagnostic dose; MK-677 is an unapproved compound taken daily, and its long-term trial found a heart failure signal." } ], "tags": [ "growth hormone", "diagnostic", "oral", "approved", "ghrelin" ] }, { "slug": "matrixyl", "name": "Matrixyl (Palmitoyl Pentapeptide-4)", "aka": [ "Pal-KTTKS", "Matrixyl 3000 (with Pal-GHK)" ], "category": "cosmetic", "chemClass": "Lipidated pentapeptide — a collagen fragment conjugated to palmitic acid", "route": "Topical", "halfLife": "Not applicable — topical", "status": "cosmetic", "statusNote": "Established cosmetic ingredient with published controlled human studies, including a comparison against retinol.", "evidence": 3, "summary": "A fragment of type I collagen that signals to fibroblasts that collagen has been damaged, prompting them to make more. The palmitoyl tail is what lets it actually get through the skin barrier — a design detail many peptide cosmetics neglect.", "mechanism": "The KTTKS sequence is a subfragment of type I procollagen. Applied topically it acts as a feedback signal stimulating fibroblast synthesis of collagen I, collagen III, fibronectin and glycosaminoglycans. Palmitoylation greatly increases lipophilicity and stratum corneum penetration.", "studied": "A 12-week double-blind split-face trial versus vehicle; a comparative study against retinol; multiple fibroblast and ex-vivo skin studies.", "benefits": [ { "t": "Wrinkle and roughness improvement in controlled trials", "d": "A 12-week double-blind trial showed significant improvement in wrinkle depth and skin roughness versus vehicle.", "s": "moderate" }, { "t": "Comparable to retinol with better tolerance", "d": "Comparative work suggests effects approaching retinol's with markedly less irritation.", "s": "moderate" }, { "t": "Collagen and matrix stimulation", "d": "Consistent fibroblast data showing upregulation of collagen and extracellular matrix components.", "s": "moderate" }, { "t": "Designed for skin penetration", "d": "The palmitoyl chain solves the delivery problem that limits many topical peptides.", "s": "moderate" }, { "t": "Very well tolerated", "d": "Suitable for sensitive skin and usable alongside most actives.", "s": "strong" } ], "risks": [ { "t": "Modest effect sizes", "d": "Real but incremental; it will not match procedural interventions.", "s": "low" }, { "t": "Slow onset", "d": "Meaningful changes take 8–12 weeks of consistent use.", "s": "low" }, { "t": "Concentration varies widely between products", "d": "Many products contain far less than the concentrations used in studies.", "s": "moderate" }, { "t": "Industry-funded research", "d": "Much of the evidence originates with ingredient suppliers.", "s": "moderate" }, { "t": "Rare contact sensitivity", "d": "Uncommon.", "s": "low" } ], "avoid": [ "Known ingredient allergy" ], "monitoring": [ "None required" ], "legal": "Lawful cosmetic ingredient.", "evidenceNotes": [ "Among the best-supported topical cosmetic peptides, with a double-blind vehicle-controlled trial." ], "tags": [ "skin", "collagen", "topical", "cosmetic", "anti-aging" ] }, { "slug": "mazdutide", "name": "Mazdutide", "aka": [ "IBI362", "LY3305677" ], "category": "metabolic", "chemClass": "Dual glucagon / GLP-1 receptor agonist based on oxyntomodulin", "route": "Subcutaneous, once weekly", "halfLife": "~5–7 days", "status": "limited", "statusNote": "Approved in China for weight management and type 2 diabetes. Not approved in the US, EU or UK.", "evidence": 4, "summary": "Built on the backbone of oxyntomodulin, a naturally occurring gut hormone that hits both the GLP-1 and glucagon receptors. It is the first of the glucagon co-agonists to reach approval anywhere, in China, ahead of the Western programs.", "mechanism": "Oxyntomodulin-derived dual agonism at the GLP-1 and glucagon receptors, reproducing an endogenous signalling pattern rather than engineering one from scratch. Appetite suppression plus increased energy expenditure and hepatic fat oxidation.", "studied": "GLORY and DREAMS phase 3 programs in Chinese populations for obesity and type 2 diabetes.", "benefits": [ { "t": "Phase 3 weight loss with regulatory approval", "d": "Phase 3 trials supported approval in China, with mean weight reductions in the mid-teens percent range at the higher dose.", "s": "strong" }, { "t": "Glycemic control in type 2 diabetes", "d": "Separate phase 3 program demonstrated HbA1c reduction sufficient for a diabetes indication.", "s": "strong" }, { "t": "Liver fat reduction", "d": "Consistent with the glucagon component; reported across trials.", "s": "moderate" }, { "t": "Endogenous hormone template", "d": "Derived from oxyntomodulin rather than a synthetic chimera, which may explain its tolerability profile.", "s": "moderate" } ], "risks": [ { "t": "No FDA or EMA approval", "d": "Approval is limited to China. Western regulators have not reviewed the dossier.", "s": "moderate" }, { "t": "Trial populations may not generalise", "d": "The phase 3 program was conducted largely in Chinese participants, who differ in baseline BMI and metabolic phenotype from Western obesity populations.", "s": "moderate" }, { "t": "GI adverse effects", "d": "Nausea, diarrhea and vomiting, dose-related as with the whole class.", "s": "moderate" }, { "t": "Heart rate increase", "d": "Class effect of glucagon co-agonism.", "s": "moderate" }, { "t": "Grey-market import", "d": "Widely sold to Western buyers outside any lawful channel.", "s": "high" } ], "avoid": [ "Medullary thyroid carcinoma or MEN2 history", "Pregnancy", "Prior pancreatitis (relative)" ], "monitoring": [ "HbA1c and weight", "Heart rate", "Hydration and renal function during GI illness" ], "legal": "Prescription medicine in China. Unapproved elsewhere; import for personal use is legally constrained.", "evidenceNotes": [ "Genuine phase 3 evidence and a real approval — but in one jurisdiction only." ], "interactions": [ "Insulin and sulfonylureas — dose reduction usually required", "Oral drugs sensitive to gastric emptying rate" ], "tags": [ "weight loss", "diabetes", "glucagon", "China-approved", "oxyntomodulin" ] }, { "slug": "melanotan-ii", "name": "Melanotan II", "aka": [ "MT-II", "MT2" ], "category": "sexual", "chemClass": "Non-selective melanocortin receptor agonist (MC1R/MC3R/MC4R/MC5R)", "route": "Subcutaneous (illicit)", "halfLife": "~1–2 hours", "status": "research", "statusNote": "Not approved anywhere. Regulators in the US, UK, Australia and across the EU have issued explicit consumer safety warnings against it.", "evidence": 1, "summary": "Sold as the \"Barbie drug\" for tanning without sun exposure. It is the clearest example on this site of a peptide where the documented harms are concrete and the regulatory position is unanimous.", "mechanism": "Non-selective melanocortin agonism. MC1R activation drives melanogenesis (the tanning effect), MC4R activation produces the appetite suppression and sexual arousal effects, and MC5R and other receptor activity accounts for much of the unpredictable side-effect profile.", "studied": "Early academic studies of tanning and sexual function in the 1990s. No completed development program; superseded by the selective and approved afamelanotide.", "benefits": [ { "t": "Produces tanning without UV", "d": "The MC1R effect is real and reliable — melanogenesis without sun exposure.", "s": "preliminary" }, { "t": "Appetite suppression", "d": "MC4R-mediated; reported consistently by users.", "s": "preliminary" }, { "t": "Sexual arousal effects", "d": "The observation that led to the development of PT-141, which is the approved and far better-characterised alternative.", "s": "preliminary" } ], "risks": [ { "t": "Melanoma and changing moles", "d": "Multiple case reports describe new or rapidly changing melanocytic lesions and melanoma diagnoses in users. It stimulates the exact cells involved.", "s": "high" }, { "t": "Rhabdomyolysis", "d": "Case reports of severe rhabdomyolysis with acute kidney injury following use.", "s": "high" }, { "t": "Priapism", "d": "Prolonged painful erection requiring emergency intervention has been reported; untreated priapism causes permanent damage.", "s": "high" }, { "t": "Severe nausea and vomiting", "d": "Very common and often severe, particularly with the first doses.", "s": "moderate" }, { "t": "Uncontrolled and unpredictable dosing", "d": "Sold as unregulated powder requiring self-reconstitution, with no standardised dose.", "s": "high" }, { "t": "Regulator warnings worldwide", "d": "FDA, MHRA, TGA and EU authorities have all warned consumers specifically against this product.", "s": "high" }, { "t": "Injection-related infection", "d": "Non-sterile reconstitution and repeated self-injection have caused abscesses and systemic infection.", "s": "high" } ], "avoid": [ "Everyone — regulators globally advise against use. Anyone with atypical naevi, melanoma history or fair skin faces particularly elevated risk" ], "monitoring": [ "If used despite advice: dermatologic surveillance with full-body skin examination" ], "legal": "Illegal to sell for human use in the US, UK, EU and Australia. Not approved anywhere.", "evidenceNotes": [ "A rare case where the harm literature is more developed than the benefit literature." ], "tags": [ "tanning", "melanocortin", "high risk", "regulator warnings", "illegal" ], "confusedWith": [ { "slug": "afamelanotide", "why": "The critical distinction on this site. Afamelanotide (Melanotan I) is a selective MC1R agonist, FDA-approved, delivered as a physician-implanted device for a rare photosensitivity disease. Melanotan II is non-selective, unapproved, self-injected, and the subject of worldwide regulator warnings including melanoma case reports." }, { "slug": "pt-141", "why": "PT-141 was developed from Melanotan II specifically to isolate the sexual-arousal effect without the pigmentation effect. PT-141 is FDA-approved for one indication; Melanotan II is approved nowhere." } ] }, { "slug": "mk-677", "name": "MK-677 (Ibutamoren)", "aka": [ "Ibutamoren", "Nutrobal", "L-163,191" ], "category": "growth", "chemClass": "Non-peptide, orally active ghrelin receptor agonist — listed here because it is universally marketed alongside peptides", "route": "Oral, once daily", "halfLife": "~4–6 hours (effects persist ~24h)", "status": "nonpeptide", "statusNote": "Not a peptide. Investigational drug; development discontinued. Not approved. Prohibited in sport.", "evidence": 3, "summary": "Technically a spiropiperidine, not a peptide — but it sits in every peptide catalogue, so it belongs here. It has more human trial data than most peptides on this page, and that data includes the reason it was abandoned.", "mechanism": "Orally bioavailable ghrelin receptor agonist producing sustained increases in GH and IGF-1 without injection. The sustained rather than pulsatile elevation is central to both its effects and its problems.", "studied": "Multiple phase 2 trials including elderly hip-fracture recovery, sarcopenia, GH deficiency, and a 2-year trial in healthy older adults.", "benefits": [ { "t": "Reliable IGF-1 elevation, orally", "d": "Trials consistently show IGF-1 increases into the young-adult range in older subjects — no injection required.", "s": "strong" }, { "t": "Increases fat-free mass", "d": "A 2-year randomized trial in healthy older adults showed a roughly 1.6 kg increase in fat-free mass versus placebo.", "s": "strong" }, { "t": "Improved sleep architecture", "d": "Studies show increased slow-wave and REM sleep duration.", "s": "moderate" }, { "t": "Appetite stimulation", "d": "Substantial, and potentially useful in cachexia or during recovery from illness.", "s": "moderate" }, { "t": "Increased bone turnover markers", "d": "Suggests bone remodelling activity, though fracture-reduction benefit was not demonstrated.", "s": "preliminary" } ], "risks": [ { "t": "Failed its key clinical trial", "d": "The hip-fracture recovery program did not meet endpoints, and development was stopped. Fat-free mass gains did not translate into functional benefit.", "s": "high" }, { "t": "Congestive heart failure signal", "d": "A trial in frail elderly patients was halted after an increase in congestive heart failure cases in the treatment arm. This is the most serious concern with the compound.", "s": "high" }, { "t": "Insulin resistance and hyperglycemia", "d": "Consistent and dose-dependent; fasting glucose rises and insulin sensitivity falls.", "s": "high" }, { "t": "Fluid retention and oedema", "d": "Common, sometimes marked, especially early in use.", "s": "moderate" }, { "t": "Increased appetite and weight gain", "d": "Often unwanted; a substantial fraction of gained weight is not lean tissue.", "s": "moderate" }, { "t": "Lethargy and joint pain", "d": "Frequently reported by users at higher doses.", "s": "low" }, { "t": "Sold illegally as a supplement", "d": "FDA has issued warning letters; it is not a lawful dietary ingredient. Prohibited by WADA.", "s": "high" } ], "avoid": [ "Any heart failure history", "Diabetes or prediabetes", "Active malignancy", "Pregnancy", "Tested athletes" ], "monitoring": [ "Fasting glucose, HbA1c, insulin", "IGF-1", "Weight and oedema", "Cardiac symptoms" ], "legal": "Unapproved investigational drug. Not lawful as a dietary supplement in the US. WADA-prohibited.", "evidenceNotes": [ "Unusually good human evidence for this category — including the negative results that ended development." ], "tags": [ "growth hormone", "oral", "not a peptide", "IGF-1", "discontinued" ], "interactions": [ "Insulin and antidiabetic drugs — MK-677 consistently worsens insulin sensitivity and raises fasting glucose", "Corticosteroids — additive metabolic effects", "Drugs for heart failure — the compound is associated with a congestive heart failure signal and should be avoided in this population" ] }, { "slug": "mots-c", "name": "MOTS-c", "aka": [ "Mitochondrial ORF of the 12S rRNA type-c" ], "category": "longevity", "chemClass": "Mitochondrial-derived peptide — 16 amino acids encoded in mitochondrial DNA", "route": "Subcutaneous (research)", "halfLife": "Short; not well characterised in humans", "status": "research", "statusNote": "Not approved. Active academic research subject; no completed human efficacy trials.", "evidence": 1, "summary": "A genuinely interesting discovery — a hormone encoded by the mitochondrial genome rather than the nucleus. The exercise-mimetic and metabolic findings in mice are striking. Human data begins and ends with observational plasma-level associations.", "mechanism": "Translocates to the nucleus under metabolic stress and regulates adaptive nuclear gene expression, notably via AMPK activation and the folate-methionine cycle. Improves insulin sensitivity and glucose utilisation in skeletal muscle in animal models.", "studied": "Mouse metabolic and exercise studies; human observational work correlating plasma MOTS-c with metabolic health, exercise and longevity phenotypes.", "benefits": [ { "t": "Improved insulin sensitivity in mice", "d": "Reverses diet-induced insulin resistance and obesity in rodent models.", "s": "preliminary" }, { "t": "Exercise-mimetic effects in animals", "d": "Improves running capacity and muscle metabolic function in aged mice.", "s": "preliminary" }, { "t": "Association with longevity variants", "d": "A mitochondrial DNA variant affecting MOTS-c is associated with exceptional longevity in a Japanese population — a real human genetic finding.", "s": "preliminary" }, { "t": "Rises with exercise in humans", "d": "Plasma MOTS-c increases acutely with exercise, consistent with a role in metabolic adaptation.", "s": "preliminary" } ], "risks": [ { "t": "No human interventional trials", "d": "Nobody has run a controlled trial of administering MOTS-c to people. All human data is correlational.", "s": "high" }, { "t": "Unknown dosing and pharmacokinetics", "d": "Circulating protocols are invented, not derived from human PK data.", "s": "high" }, { "t": "Broad transcriptional effects", "d": "A peptide that alters nuclear gene expression programs has correspondingly broad potential for unintended consequences.", "s": "moderate" }, { "t": "Unregulated supply", "d": "Research-chemical market.", "s": "high" } ], "avoid": [ "Human use outside research settings" ], "monitoring": [ "No validated monitoring exists" ], "legal": "Not approved for human use.", "evidenceNotes": [ "Legitimate and active academic science; zero human interventional evidence." ], "tags": [ "mitochondria", "metabolic", "exercise mimetic", "longevity", "preclinical only" ] }, { "slug": "nesiritide", "name": "Nesiritide", "aka": [ "Natrecor", "recombinant BNP" ], "category": "cardiac", "chemClass": "Recombinant human B-type natriuretic peptide — 32 amino acids", "route": "Intravenous infusion", "halfLife": "~18 minutes", "status": "approved", "statusNote": "FDA-approved (2001) for acutely decompensated heart failure. Use collapsed after a large trial showed no benefit on clinical outcomes.", "evidence": 5, "summary": "A cautionary tale worth reading before trusting any surrogate endpoint. Nesiritide was approved because it improved breathlessness scores and lowered filling pressures. When a 7,000-patient trial finally asked whether patients did better, the answer was no.", "mechanism": "Identical to endogenous BNP. Binds natriuretic peptide receptor A, raising cyclic GMP to produce venous and arterial vasodilation, natriuresis and diuresis, and suppression of the renin-angiotensin-aldosterone and sympathetic systems.", "studied": "VMAC trial (approval basis, dyspnoea and haemodynamic endpoints); ASCEND-HF, a 7,141-patient outcomes trial.", "benefits": [ { "t": "Reduces pulmonary capillary wedge pressure", "d": "Rapid and reliable haemodynamic improvement — the physiology works exactly as designed.", "s": "strong" }, { "t": "Small improvement in dyspnoea", "d": "ASCEND-HF found a statistically significant but clinically marginal improvement in self-reported breathlessness.", "s": "moderate" }, { "t": "No proarrhythmia", "d": "Unlike inotropes such as milrinone or dobutamine, it does not increase arrhythmia burden.", "s": "strong" }, { "t": "Validated the natriuretic peptide axis", "d": "The pathway itself proved therapeutically real, and was later exploited successfully by neprilysin inhibition.", "s": "moderate" } ], "risks": [ { "t": "No benefit on death or rehospitalisation", "d": "ASCEND-HF found no reduction in 30-day mortality or heart failure rehospitalisation. The surrogate endpoints that won approval did not translate.", "s": "high" }, { "t": "Hypotension", "d": "Significantly more common than with placebo, and often prolonged given the vasodilator mechanism.", "s": "high" }, { "t": "Earlier renal safety controversy", "d": "Meta-analyses raised concerns about worsening renal function; ASCEND-HF did not confirm renal harm but did not vindicate the drug either.", "s": "moderate" }, { "t": "High cost for no outcome benefit", "d": "Substantially more expensive than nitroglycerin, which performs comparably.", "s": "moderate" }, { "t": "Largely abandoned in practice", "d": "Guidelines no longer recommend routine use, and clinical use has collapsed.", "s": "moderate" } ], "avoid": [ "Cardiogenic shock", "Systolic blood pressure below 90 mmHg", "Suspected low filling pressures", "Valvular stenosis or constrictive pericarditis" ], "monitoring": [ "Continuous blood pressure monitoring", "Renal function and electrolytes", "Symptom response and fluid balance" ], "legal": "Prescription drug; approval retained but clinical use is minimal.", "evidenceNotes": [ "An approval based on surrogate endpoints, overturned in practice by a large outcomes trial — one of the best-documented examples in cardiology." ], "interactions": [ "ACE inhibitors — additive hypotension", "Other vasodilators — additive hypotension", "Note: BNP assays are confounded during infusion; NT-proBNP is unaffected" ], "tags": [ "heart failure", "natriuretic peptide", "approved", "failed outcomes trial", "surrogate endpoints" ] }, { "slug": "noopept", "name": "Noopept", "aka": [ "N-phenylacetyl-L-prolylglycine ethyl ester", "GVS-111", "Omberacetam" ], "category": "cognitive", "chemClass": "Dipeptide-derived nootropic — a proline-containing dipeptide ethyl ester", "route": "Oral or sublingual", "halfLife": "~16–30 minutes (active metabolite cycloprolylglycine persists longer)", "status": "limited", "statusNote": "Registered as a prescription medicine in Russia. In the US, FDA has determined it is not a lawful dietary ingredient. Not approved in the EU or UK.", "evidence": 2, "summary": "Widely sold in the West as a nootropic supplement despite being a prescription drug in its country of origin and explicitly excluded from the US supplement category. Its Russian trial record is more substantial than most nootropics and still falls well short of Western standards.", "mechanism": "Rapidly metabolised to cycloprolylglycine, an endogenous neuropeptide. Reported effects include increased BDNF and NGF expression in the hippocampus, modulation of AMPA and NMDA receptor function, and antioxidant activity. Structurally related to the racetam family but active at far lower doses.", "studied": "Russian randomized trials in mild cognitive impairment of vascular and post-traumatic origin; extensive Russian preclinical work.", "benefits": [ { "t": "Reported cognitive benefit in mild impairment", "d": "Russian randomized trials described improvement in cognitive and affective symptoms in vascular and post-traumatic cognitive impairment.", "s": "preliminary" }, { "t": "Neurotrophin upregulation", "d": "Documented increases in hippocampal BDNF and NGF expression in animal models.", "s": "preliminary" }, { "t": "Active at low doses", "d": "Roughly a thousandfold more potent by weight than piracetam.", "s": "preliminary" }, { "t": "Anxiolytic component reported", "d": "Russian studies describe reduced anxiety and irritability alongside cognitive effects.", "s": "preliminary" } ], "risks": [ { "t": "Not a lawful supplement in the US", "d": "FDA has stated it does not meet the dietary ingredient definition, making its sale as a supplement unlawful — a fact most vendors omit.", "s": "high" }, { "t": "Evidence base not independently replicated", "d": "No Western randomized trials exist. Methodological standards in the source literature are inconsistent.", "s": "high" }, { "t": "Irritability, headache and sleep disruption", "d": "Commonly reported, particularly at higher doses or later in the day.", "s": "moderate" }, { "t": "Blood pressure elevation", "d": "Reported in some users; caution advised in hypertension.", "s": "moderate" }, { "t": "No long-term safety data", "d": "Chronic use has not been characterised outside Russian practice.", "s": "moderate" }, { "t": "Product quality varies widely", "d": "Sold by supplement vendors with inconsistent purity and labelling.", "s": "moderate" } ], "avoid": [ "Pregnancy and breastfeeding", "Uncontrolled hypertension", "Severe hepatic or renal impairment", "Concurrent stimulants without medical supervision" ], "monitoring": [ "Blood pressure", "Sleep quality and mood", "Cognitive assessment if used for impairment" ], "legal": "Prescription medicine in Russia. Not a lawful dietary supplement in the US. Unapproved in the EU and UK.", "evidenceNotes": [ "More Russian trial data than most nootropics, and no independent Western replication." ], "confusedWith": [ { "slug": "semax", "why": "Both are Russian-developed neuropeptides sold as nootropics in the West. Semax is a seven-residue ACTH fragment given intranasally; noopept is an orally active dipeptide ester. Neither has Western regulatory review." } ], "tags": [ "nootropic", "BDNF", "Russia-approved", "oral", "unlawful supplement" ] }, { "slug": "orforglipron", "name": "Orforglipron", "aka": [ "LY3502970" ], "category": "metabolic", "chemClass": "Non-peptide small-molecule GLP-1 receptor agonist — orally bioavailable", "route": "Oral, once daily", "halfLife": "~29–49 hours", "status": "trials", "statusNote": "Not a peptide. Phase 3 (ATTAIN and ACHIEVE programs). Not approved at the time of review.", "evidence": 4, "summary": "Included because it may make injectable peptides obsolete for most people. It is a small molecule, not a peptide, so it survives digestion without the absorption enhancers and strict fasting rules that oral semaglutide requires.", "mechanism": "Binds the GLP-1 receptor at a site accessible to a small molecule, producing incretin signalling without a peptide backbone. Because it is not degraded by gut proteases, it needs no permeation enhancer and has no food or water restrictions.", "studied": "Phase 3 ATTAIN trials in obesity and ACHIEVE trials in type 2 diabetes; multiple phase 2 trials preceding them.", "benefits": [ { "t": "Injection-free GLP-1 therapy", "d": "A daily tablet with no fasting window removes the single largest barrier to incretin therapy for most patients.", "s": "strong" }, { "t": "Weight loss in the GLP-1 range", "d": "Phase 3 obesity results showed mean weight reduction broadly comparable to injectable semaglutide.", "s": "strong" }, { "t": "Manufacturing scale", "d": "Small-molecule synthesis avoids the peptide manufacturing bottleneck that has caused repeated GLP-1 shortages.", "s": "moderate" }, { "t": "No food or water restrictions", "d": "Unlike oral semaglutide, which requires dosing fasted with a strict water volume and a 30-minute wait.", "s": "strong" } ], "risks": [ { "t": "Not approved at the time of this review", "d": "Regulatory decisions were pending; nothing here should be read as an approval.", "s": "high" }, { "t": "GI adverse effects persist", "d": "Nausea, vomiting and diarrhea occur at rates comparable to injectable GLP-1 agonists — the route changed, the receptor did not.", "s": "moderate" }, { "t": "Daily dosing adherence", "d": "A daily tablet is easier to start and easier to forget than a weekly injection.", "s": "low" }, { "t": "Class contraindications still apply", "d": "Thyroid C-cell and pancreatitis cautions are receptor-driven, not formulation-driven.", "s": "high" }, { "t": "Not a peptide", "d": "Listed here for context. Do not assume peptide-specific information applies to it.", "s": "low" } ], "avoid": [ "Medullary thyroid carcinoma or MEN2 history", "Pregnancy", "Prior pancreatitis (relative)" ], "monitoring": [ "HbA1c, weight", "GI tolerability during titration" ], "legal": "Investigational at the time of review. Check current FDA status before relying on this page.", "evidenceNotes": [ "Large phase 3 program with active and placebo comparators.", "Regulatory status is the fastest-moving fact on this page." ], "interactions": [ "Insulin and sulfonylureas — hypoglycemia risk", "Fewer absorption interactions than oral semaglutide, since it needs no permeation enhancer" ], "tags": [ "weight loss", "oral", "not a peptide", "GLP-1", "investigational" ] }, { "slug": "oxytocin", "name": "Oxytocin", "aka": [ "Pitocin", "Syntocinon" ], "category": "hormonal", "chemClass": "Endogenous nonapeptide hormone", "route": "Intravenous (approved obstetric use); intranasal (research and off-label)", "halfLife": "~1–6 minutes intravenously", "status": "approved", "statusNote": "FDA-approved for labor induction and postpartum hemorrhage control. Intranasal use for social, psychiatric and relationship indications is off-label and not supported by consistent trial evidence.", "evidence": 5, "summary": "Two very different stories in one molecule. As an obstetric drug it is essential medicine with a boxed warning. As the \"love hormone\" delivered by nasal spray, the trial record has been consistently disappointing.", "mechanism": "Binds oxytocin receptors on uterine smooth muscle to produce contractions, and on myoepithelial cells for milk ejection. Central oxytocin signalling modulates social cognition, trust and pair bonding — but how much intranasally administered oxytocin actually reaches relevant brain regions remains genuinely contested.", "studied": "Extensive obstetric use and trials; numerous randomized trials of intranasal oxytocin in autism spectrum disorder, schizophrenia, PTSD and social anxiety, with predominantly negative or inconsistent results.", "benefits": [ { "t": "Effective labor induction and augmentation", "d": "A cornerstone obstetric drug with decades of established efficacy.", "s": "strong" }, { "t": "Postpartum hemorrhage control", "d": "First-line uterotonic; a major contributor to reduced maternal mortality worldwide.", "s": "strong" }, { "t": "Milk ejection reflex support", "d": "Established physiological role in lactation.", "s": "strong" }, { "t": "Some social cognition signals", "d": "Early studies suggested effects on trust and emotion recognition; larger and better-controlled trials have largely not replicated them.", "s": "preliminary" } ], "risks": [ { "t": "Boxed warning against elective induction", "d": "The label explicitly warns against use for elective labor induction due to risks of uterine rupture and fetal distress.", "s": "high" }, { "t": "Water intoxication and hyponatremia", "d": "Structural similarity to vasopressin gives antidiuretic activity; severe hyponatremia and seizures have occurred with high-dose infusion.", "s": "high" }, { "t": "Uterine hyperstimulation and rupture", "d": "A serious obstetric complication requiring continuous fetal monitoring.", "s": "high" }, { "t": "Intranasal social claims largely unreplicated", "d": "The large multi-site autism trial was negative. The popular framing outran the evidence considerably.", "s": "moderate" }, { "t": "Uncertain CNS delivery", "d": "How much intranasal oxytocin reaches the brain, and in what concentration, remains a live scientific dispute.", "s": "moderate" }, { "t": "Cardiovascular effects with rapid IV administration", "d": "Hypotension and tachycardia can occur with bolus dosing.", "s": "moderate" } ], "avoid": [ "Elective labor induction", "Cephalopelvic disproportion and other obstetric contraindications", "Unsupervised intranasal use for psychiatric conditions" ], "monitoring": [ "Continuous fetal and uterine monitoring during obstetric use", "Serum sodium with prolonged infusion", "Fluid balance" ], "legal": "Prescription drug for approved obstetric indications. Compounded intranasal oxytocin is off-label.", "evidenceNotes": [ "Strong obstetric evidence; a notable and instructive replication failure in the social neuroscience literature." ], "tags": [ "obstetric", "social", "bonding", "approved", "replication failure" ], "interactions": [ "Vasoconstrictors and ergot alkaloids — severe hypertension has been reported", "Prostaglandins — potentiate uterine activity; careful sequencing required", "Volatile anesthetics — can reduce uterine response and cause hypotension", "Large-volume hypotonic fluids — compound the risk of water intoxication" ], "confusedWith": [ { "slug": "desmopressin", "why": "Oxytocin and vasopressin differ by two amino acids, which is why high-dose oxytocin causes water retention and hyponatremia. Desmopressin is the engineered V2-selective vasopressin analog." } ] }, { "slug": "palmitoyl-tripeptide-1", "name": "Palmitoyl Tripeptide-1", "aka": [ "Pal-GHK", "Matrixyl Synthe'6 component", "palmitoyl oligopeptide" ], "category": "cosmetic", "chemClass": "Lipidated tripeptide — the GHK sequence conjugated to palmitic acid", "route": "Topical", "halfLife": "Not applicable — topical", "status": "cosmetic", "statusNote": "Widely used cosmetic ingredient, typically paired with palmitoyl tetrapeptide-7 in commercial formulations.", "evidence": 3, "summary": "The same GHK sequence as the copper peptide, but with a fatty tail instead of a copper ion. That change trades the copper-delivery mechanism for much better skin penetration, and it is almost always sold combined with a second peptide that targets inflammation.", "mechanism": "The GHK tripeptide signals fibroblasts to increase collagen, elastin and glycosaminoglycan synthesis. Palmitoylation raises lipophilicity so the peptide crosses the stratum corneum, which unmodified GHK does poorly. The commonly paired palmitoyl tetrapeptide-7 reduces interleukin-6 production, addressing inflammatory matrix breakdown by a separate route.", "studied": "Controlled topical studies of the combination product measuring wrinkle depth and dermal density; fibroblast and ex-vivo skin work.", "benefits": [ { "t": "Wrinkle depth reduction in controlled studies", "d": "Combination products showed measurable improvement in wrinkle depth and skin smoothness versus vehicle over 8–12 weeks.", "s": "moderate" }, { "t": "Collagen and matrix stimulation", "d": "Consistent fibroblast data for increased collagen I, III and IV, plus fibronectin and hyaluronic acid.", "s": "moderate" }, { "t": "Better penetration than unmodified GHK", "d": "The palmitoyl chain solves the delivery problem that limits most topical peptides.", "s": "moderate" }, { "t": "Complementary anti-inflammatory partner", "d": "The paired tetrapeptide-7 targets IL-6-driven matrix degradation, a different mechanism from collagen stimulation.", "s": "moderate" }, { "t": "Very well tolerated", "d": "Suitable for sensitive skin and compatible with most other actives.", "s": "strong" } ], "risks": [ { "t": "Effect sizes are modest", "d": "Real but incremental. It will not approach the results of retinoids at effective concentrations, or procedural treatments.", "s": "low" }, { "t": "Evidence largely from ingredient suppliers", "d": "Most supporting studies are manufacturer-sponsored, and independent replication is limited.", "s": "moderate" }, { "t": "Combination products obscure attribution", "d": "Because it is nearly always sold with tetrapeptide-7, the individual contribution of each peptide is unclear.", "s": "moderate" }, { "t": "Concentration rarely disclosed", "d": "Products vary widely and often contain far less than the studied concentration.", "s": "moderate" }, { "t": "Requires continuous use", "d": "Benefits regress once application stops.", "s": "low" } ], "avoid": [ "Known ingredient allergy", "Broken or actively irritated skin" ], "monitoring": [ "None required" ], "legal": "Lawful cosmetic ingredient.", "evidenceNotes": [ "Reasonable topical evidence with the usual cosmetic-industry funding caveat." ], "confusedWith": [ { "slug": "ghk-cu", "why": "Same GHK tripeptide, different delivery. GHK-Cu carries a copper ion and works partly through copper delivery; palmitoyl tripeptide-1 carries a fatty tail for penetration and has no copper component." }, { "slug": "matrixyl", "why": "Matrixyl is palmitoyl pentapeptide-4 (Pal-KTTKS). \"Matrixyl 3000\" and \"Synthe'6\" are different blends that include palmitoyl tripeptide-1. The names are marketing, not chemistry." } ], "tags": [ "skin", "collagen", "topical", "cosmetic", "GHK" ] }, { "slug": "pentadeca-arginate", "name": "Pentadeca Arginate (PDA)", "aka": [ "PDA", "BPC-157 arginate salt", "Pentadecapeptide arginate" ], "category": "healing", "chemClass": "Arginate salt form of the BPC-157 pentadecapeptide", "route": "Subcutaneous (research)", "halfLife": "Not established", "status": "research", "statusNote": "Not approved. Marketed as a \"legal alternative\" after BPC-157 was barred from compounding — a claim regulators have not endorsed.", "evidence": 1, "summary": "Commercially, PDA exists because BPC-157 was banned from compounding. Chemically it is the same peptide with a different counter-ion. The marketing implies improved stability and a cleaner legal status; neither claim has independent evidence behind it.", "mechanism": "Identical peptide sequence to BPC-157, formulated as an arginate salt which is claimed to improve stability and absorption. The underlying biological mechanism — if any — is whatever BPC-157 does.", "studied": "No published clinical trials. No independent peer-reviewed characterisation of the salt form versus the acetate form.", "benefits": [ { "t": "Possible improved stability", "d": "Salt selection can genuinely affect peptide shelf stability, though the specific claims for PDA come from vendors rather than published data.", "s": "preliminary" }, { "t": "Shares BPC-157 preclinical rationale", "d": "Any preclinical support is inherited from the BPC-157 literature, not generated independently.", "s": "preliminary" } ], "risks": [ { "t": "Zero independent evidence", "d": "There is no published study of PDA as such — not in humans, and not head-to-head against BPC-157 in animals.", "s": "high" }, { "t": "Regulatory workaround, not a regulatory clearance", "d": "Renaming or re-salting a substance barred from compounding does not make it approved. Buyers frequently misread it as legitimised.", "s": "high" }, { "t": "Inherits every BPC-157 concern", "d": "Including the angiogenesis-and-cancer question and the absence of chronic safety data.", "s": "high" }, { "t": "Unverified product identity", "d": "Analytical testing of what is actually in these vials is not routinely available to buyers.", "s": "high" } ], "avoid": [ "Cancer history or undiagnosed mass", "Pregnancy and breastfeeding", "Tested athletes" ], "monitoring": [ "No validated monitoring exists" ], "legal": "Not approved. Marketing it as a compliant substitute for a substance FDA excluded from compounding is legally precarious.", "evidenceNotes": [ "Included on this site because it is heavily marketed, not because evidence supports it." ], "tags": [ "tendon", "injury recovery", "BPC-157", "marketing", "research chemical" ], "confusedWith": [ { "slug": "bpc-157", "why": "Chemically the same peptide with a different counter-ion. PDA is marketed as a lawful alternative to a substance FDA excluded from compounding; that is a commercial framing, not a regulatory clearance." } ] }, { "slug": "plecanatide", "name": "Plecanatide", "aka": [ "Trulance" ], "category": "gut", "chemClass": "Guanylate cyclase-C agonist — 16-amino-acid uroguanylin analog", "route": "Oral tablet, once daily", "halfLife": "Minimally absorbed — acts locally", "status": "approved", "statusNote": "FDA-approved for chronic idiopathic constipation and for irritable bowel syndrome with constipation.", "evidence": 4, "summary": "Linaclotide's younger sibling, designed around the body's own uroguanylin rather than a bacterial toxin. Its distinguishing feature is pH-dependence: it is most active in the slightly acidic proximal small intestine and loses activity further down, which is intended to limit diarrhea.", "mechanism": "Agonises guanylate cyclase-C, increasing cyclic GMP and driving chloride and bicarbonate secretion into the lumen. Unlike linaclotide, which derives from heat-stable enterotoxin, plecanatide is a near-copy of endogenous uroguanylin and retains its pH-sensitivity, binding maximally around pH 5.", "studied": "Phase 3 trials in chronic idiopathic constipation and in IBS-C.", "benefits": [ { "t": "Phase 3 efficacy in both indications", "d": "Met primary endpoints for complete spontaneous bowel movements and for abdominal pain in IBS-C.", "s": "strong" }, { "t": "pH-dependent activity", "d": "Activity concentrated in the proximal small intestine, the rationale for a potentially gentler effect profile.", "s": "moderate" }, { "t": "Single dose strength for constipation", "d": "No titration needed for the chronic idiopathic constipation indication.", "s": "moderate" }, { "t": "Negligible systemic absorption", "d": "Like linaclotide, essentially no systemic drug interactions.", "s": "strong" } ], "risks": [ { "t": "Boxed warning: contraindicated in young children", "d": "Same class warning as linaclotide — contraindicated under 6 years, and not recommended between 6 and 18, due to fatal dehydration risk in juvenile animals.", "s": "high" }, { "t": "Diarrhea", "d": "The dominant adverse event, though rates were somewhat lower than reported for linaclotide in separate trials.", "s": "moderate" }, { "t": "No head-to-head comparison", "d": "The claim of better tolerability than linaclotide rests on cross-trial comparison, which is not reliable evidence.", "s": "moderate" }, { "t": "Contraindicated in obstruction", "d": "Same class contraindication.", "s": "high" }, { "t": "Severe dehydration risk", "d": "Stop the drug if severe diarrhea develops.", "s": "high" } ], "avoid": [ "Children under 6 years — boxed warning", "Patients aged 6 to 18 (not recommended)", "Known or suspected mechanical obstruction" ], "monitoring": [ "Stool frequency and consistency", "Hydration status", "Symptom response over 4–12 weeks" ], "legal": "Prescription drug.", "evidenceNotes": [ "Solid phase 3 evidence; the tolerability advantage over linaclotide is inferred, not demonstrated head-to-head." ], "interactions": [ "Minimal systemic interactions", "Other laxatives — additive diarrhea risk" ], "confusedWith": [ { "slug": "linaclotide", "why": "Same receptor and indications. The differences are the parent molecule (uroguanylin vs bacterial enterotoxin), pH-sensitivity, and the pediatric age cut-off in the boxed warning." } ], "tags": [ "IBS", "constipation", "oral peptide", "approved", "uroguanylin" ] }, { "slug": "pt-141", "name": "PT-141 (Bremelanotide)", "aka": [ "Bremelanotide", "Vyleesi" ], "category": "sexual", "chemClass": "Melanocortin receptor agonist (MC3R/MC4R) — cyclic heptapeptide", "route": "Subcutaneous autoinjector, as needed", "halfLife": "~2.7 hours", "status": "approved", "statusNote": "FDA-approved (2019) for acquired, generalized hypoactive sexual desire disorder in premenopausal women", "evidence": 5, "summary": "The only approved drug that acts on sexual desire centrally rather than on blood flow peripherally. Approved for a specific indication in a specific population, and used far outside it — including in men, where it has never been approved.", "mechanism": "Activates melanocortin receptors in the hypothalamus, modulating dopaminergic pathways involved in sexual desire and arousal. Unlike PDE5 inhibitors, it acts on central desire circuits rather than on penile or genital vascular smooth muscle.", "studied": "RECONNECT phase 3 trials in premenopausal women with HSDD; earlier studies in erectile dysfunction including an intranasal formulation that was discontinued over blood-pressure effects.", "benefits": [ { "t": "Statistically significant desire improvement", "d": "Phase 3 trials showed improvement in validated desire and distress scores versus placebo, sufficient for FDA approval.", "s": "strong" }, { "t": "On-demand rather than daily dosing", "d": "Taken ahead of anticipated activity, unlike flibanserin which requires continuous daily use.", "s": "strong" }, { "t": "Central mechanism", "d": "Addresses desire directly, useful where vascular-acting drugs are irrelevant to the problem.", "s": "strong" }, { "t": "No alcohol interaction restriction", "d": "A practical advantage over flibanserin, which carries alcohol warnings.", "s": "moderate" } ], "risks": [ { "t": "Nausea", "d": "The dominant adverse effect — roughly 40% of patients in trials, and about 1 in 8 required an antiemetic.", "s": "moderate" }, { "t": "Transient blood pressure increase", "d": "Systolic rises of several mmHg with a compensatory heart-rate decrease. Contraindicated in uncontrolled hypertension or known cardiovascular disease.", "s": "high" }, { "t": "Hyperpigmentation with repeated dosing", "d": "Focal darkening of the face, gums and breasts occurred in trials, more often with frequent use; may be permanent. Dosing is capped at 8 doses per month partly for this reason.", "s": "moderate" }, { "t": "Modest average effect size", "d": "Statistically significant but clinically modest; response rates leave many patients unimproved.", "s": "moderate" }, { "t": "Flushing and injection-site reactions", "d": "Common but generally mild.", "s": "low" }, { "t": "Widespread off-label and grey-market use", "d": "Heavily sold as unapproved \"research PT-141\" for men and postmenopausal women — populations where efficacy and safety were not established.", "s": "high" } ], "avoid": [ "Uncontrolled hypertension", "Known cardiovascular disease", "Pregnancy", "Postmenopausal women and men (outside approved indication)" ], "monitoring": [ "Blood pressure before initiation and periodically", "Skin and gum pigmentation", "Dose frequency — no more than one dose in 24 hours, 8 per month" ], "legal": "Prescription drug for its labelled indication. \"Research grade\" PT-141 sold online is unapproved.", "evidenceNotes": [ "Two adequately powered phase 3 trials with validated patient-reported endpoints." ], "tags": [ "libido", "HSDD", "melanocortin", "approved", "sexual health" ], "interactions": [ "Antihypertensives — bremelanotide transiently raises blood pressure and can offset them", "Naltrexone — reduced exposure; concurrent use is not recommended", "Oral drugs with slow absorption — bremelanotide slows gastric emptying", "Alcohol — compounds nausea" ] }, { "slug": "retatrutide", "name": "Retatrutide", "aka": [ "LY3437943", "triple-G" ], "category": "metabolic", "chemClass": "Triple GLP-1 / GIP / glucagon receptor agonist", "route": "Subcutaneous, once weekly (investigational)", "halfLife": "~6 days", "status": "trials", "statusNote": "Phase 3 (TRIUMPH program). Not approved anywhere. Widely and illegally sold grey-market.", "evidence": 3, "summary": "Adds glucagon-receptor agonism to the incretin pair, which raises energy expenditure on top of appetite suppression. Phase 2 weight-loss results are the largest yet reported for a pharmacological agent, but long-term safety is genuinely unknown.", "mechanism": "Simultaneous agonism at three receptors. GLP-1 and GIP reduce intake and improve insulin dynamics; glucagon-receptor activation increases hepatic fat oxidation and resting energy expenditure — the same axis that makes glucagon a stress hormone, which is why cardiac and glycemic effects need close scrutiny.", "studied": "Phase 2 obesity and type 2 diabetes trials; phase 3 TRIUMPH trials ongoing across obesity, diabetes, knee osteoarthritis and sleep apnea.", "benefits": [ { "t": "Largest reported pharmacologic weight loss", "d": "Phase 2 data showed roughly 24% mean body-weight reduction at 48 weeks on the highest dose, with weight curves that had not yet plateaued.", "s": "moderate" }, { "t": "Marked hepatic fat reduction", "d": "A sub-study reported near-complete normalization of liver fat content in most participants with steatosis.", "s": "moderate" }, { "t": "Increased energy expenditure", "d": "The glucagon component adds a thermogenic mechanism absent from GLP-1-only drugs, in principle limiting metabolic adaptation.", "s": "preliminary" } ], "risks": [ { "t": "No phase 3 safety data yet", "d": "Every claim about long-term safety is extrapolation. Approval is not guaranteed and prior obesity drugs have failed at exactly this stage.", "s": "high" }, { "t": "Dose-dependent heart-rate increase", "d": "Phase 2 showed increases in heart rate that peaked mid-trial. Cardiovascular outcome data do not yet exist.", "s": "high" }, { "t": "Glucose elevation potential", "d": "Glucagon agonism can raise hepatic glucose output; net glycemic effect depends on the balance with incretin activity.", "s": "moderate" }, { "t": "Severe GI effects at high doses", "d": "Nausea and vomiting were the dominant adverse events and drove discontinuations.", "s": "moderate" }, { "t": "Entirely unregulated supply", "d": "All retatrutide sold to consumers is illicit. There is no verified identity, purity, sterility, or dose accuracy, and no recourse if harmed.", "s": "high" } ], "avoid": [ "Everyone outside a registered clinical trial — there is no lawful or quality-assured route to this compound" ], "monitoring": [ "Not applicable outside trial settings" ], "legal": "Investigational. Not approved by FDA, EMA, or any comparable regulator. Sale for human use is unlawful; \"research chemical\" labelling does not change that.", "evidenceNotes": [ "Phase 2 only, in the public domain. Phase 3 results pending.", "Peer-reviewed publication exists for phase 2 obesity data." ], "tags": [ "weight loss", "investigational", "GLP-1", "glucagon", "liver fat" ], "confusedWith": [ { "slug": "tirzepatide", "why": "Retatrutide adds glucagon-receptor agonism on top of tirzepatide's two targets. It shows larger phase 2 weight loss but has no phase 3 safety data and no approval anywhere." }, { "slug": "survodutide", "why": "Both add glucagon agonism. Survodutide is a dual agonist with a biopsy-confirmed liver endpoint in phase 2; retatrutide is a triple agonist with the larger weight-loss numbers." } ] }, { "slug": "selank", "name": "Selank", "aka": [ "TP-7", "tuftsin analog" ], "category": "cognitive", "chemClass": "Synthetic heptapeptide analog of the immunomodulatory peptide tuftsin", "route": "Intranasal (primary)", "halfLife": "Short; central effects persist longer than plasma levels", "status": "limited", "statusNote": "Registered in Russia as an anxiolytic. Not approved in the US, EU or UK.", "evidence": 2, "summary": "Semax's anxiolytic sibling, developed at the same Russian institute. It is framed as a benzodiazepine alternative without sedation, tolerance or dependence — a claim supported by Russian trials and untested elsewhere.", "mechanism": "Modulates GABA-A receptor expression indirectly, influences serotonin and noradrenaline turnover, and increases BDNF. Also inhibits enkephalin degradation, extending endogenous opioid signalling. The tuftsin backbone confers immunomodulatory activity independent of the CNS effects.", "studied": "Russian randomized comparisons against benzodiazepines in generalized anxiety disorder; preclinical anxiolytic and antidepressant models.", "benefits": [ { "t": "Anxiolysis without sedation", "d": "Russian comparative trials reported anxiety reduction comparable to medazepam without cognitive impairment or sedation.", "s": "preliminary" }, { "t": "No reported dependence or withdrawal", "d": "Unlike benzodiazepines, no tolerance or discontinuation syndrome has been described — a genuinely important distinction if it holds.", "s": "preliminary" }, { "t": "BDNF and neuroplasticity effects", "d": "Documented increases in hippocampal BDNF expression.", "s": "preliminary" }, { "t": "Immunomodulatory activity", "d": "Tuftsin-derived effects on macrophage function and cytokine balance.", "s": "preliminary" }, { "t": "Mild side-effect profile in reported use", "d": "Russian clinical experience describes few adverse events.", "s": "preliminary" } ], "risks": [ { "t": "No Western trials", "d": "The entire evidence base is Russian and largely unreplicated.", "s": "high" }, { "t": "Not a substitute for treated anxiety disorder", "d": "Substituting an unapproved peptide for validated therapy risks under-treating a serious condition.", "s": "high" }, { "t": "Unknown long-term effects", "d": "No chronic-use safety data outside Russian clinical practice.", "s": "moderate" }, { "t": "Grey-market quality", "d": "Imported product is unverified for identity and sterility.", "s": "high" }, { "t": "Nasal irritation", "d": "The most commonly reported local effect.", "s": "low" } ], "avoid": [ "Pregnancy", "Serious psychiatric illness without specialist care", "Use as a replacement for evidence-based anxiety treatment" ], "monitoring": [ "Validated anxiety scales if used clinically", "Mood and sleep tracking" ], "legal": "Prescription medicine in Russia; unapproved elsewhere.", "evidenceNotes": [ "Plausible mechanism, encouraging domestic trials, no independent confirmation." ], "tags": [ "anxiety", "nootropic", "BDNF", "intranasal", "Russia-approved" ] }, { "slug": "semaglutide", "name": "Semaglutide", "aka": [ "Ozempic", "Wegovy", "Rybelsus" ], "category": "metabolic", "chemClass": "GLP-1 receptor agonist — 31-amino-acid acylated analog of human GLP-1", "route": "Subcutaneous, once weekly (oral tablet daily formulation also marketed)", "halfLife": "~7 days (fatty-acid acylation drives albumin binding)", "status": "approved", "statusNote": "FDA-approved for type 2 diabetes, chronic weight management, and cardiovascular risk reduction in obesity", "evidence": 5, "summary": "The most heavily studied peptide in modern medicine. Semaglutide mimics the gut hormone GLP-1, slowing gastric emptying, amplifying glucose-dependent insulin release, and acting on hypothalamic appetite circuits. Phase 3 programs enrolling tens of thousands of patients support both glycemic and weight outcomes.", "mechanism": "Binds the GLP-1 receptor on pancreatic beta cells, gastric smooth muscle, and hypothalamic/hindbrain neurons. The result is glucose-dependent insulin secretion, suppressed glucagon, delayed gastric emptying, and reduced hunger and food reward signalling. Acylation with a C18 diacid chain gives albumin binding and a one-week half-life.", "studied": "STEP program (obesity), SUSTAIN program (type 2 diabetes), SELECT (cardiovascular outcomes), STEP-HFpEF (heart failure with preserved ejection fraction), FLOW (diabetic kidney disease).", "benefits": [ { "t": "Substantial, durable weight loss", "d": "In the 68-week STEP 1 trial, adults without diabetes lost roughly 15% of body weight on 2.4 mg weekly versus about 2.4% on placebo — a magnitude previously seen only with bariatric surgery.", "s": "strong" }, { "t": "Strong glycemic control", "d": "HbA1c reductions on the order of 1.5–1.8 percentage points across the SUSTAIN trials, with low intrinsic hypoglycemia risk because insulin release is glucose-dependent.", "s": "strong" }, { "t": "Cardiovascular event reduction", "d": "The SELECT trial in patients with obesity and established cardiovascular disease but no diabetes showed roughly a 20% relative reduction in major adverse cardiovascular events.", "s": "strong" }, { "t": "Kidney outcome benefit", "d": "The FLOW trial in diabetic kidney disease was stopped early for efficacy on a composite kidney endpoint.", "s": "strong" }, { "t": "Symptom relief in HFpEF", "d": "STEP-HFpEF showed clinically meaningful improvement in heart-failure symptom scores and 6-minute walk distance in obesity-related HFpEF.", "s": "moderate" }, { "t": "Reduction in liver fat", "d": "Trials in metabolic dysfunction-associated steatohepatitis show improved steatosis and inflammation, though fibrosis benefit has been harder to demonstrate.", "s": "moderate" } ], "risks": [ { "t": "Gastrointestinal intolerance", "d": "Nausea, vomiting, diarrhea and constipation affect a large minority of users — the single most common reason for stopping. Slow titration mitigates but does not eliminate it.", "s": "moderate" }, { "t": "Thyroid C-cell tumor boxed warning", "d": "Rodents developed medullary thyroid tumors. Human relevance is unproven, but the drug is contraindicated with a personal or family history of medullary thyroid carcinoma or MEN2.", "s": "high" }, { "t": "Pancreatitis and gallbladder disease", "d": "Acute pancreatitis is uncommon but reported. Rapid weight loss raises the rate of cholelithiasis and cholecystitis.", "s": "high" }, { "t": "Loss of lean mass", "d": "A meaningful share of total weight lost is fat-free mass. Resistance training and adequate protein intake are standard mitigation, not optional extras.", "s": "moderate" }, { "t": "Delayed gastric emptying and anesthesia risk", "d": "Retained gastric contents have prompted anesthesia societies to issue pre-procedural fasting and withholding guidance because of aspiration risk.", "s": "moderate" }, { "t": "Retinopathy worsening with rapid glycemic drop", "d": "Observed in SUSTAIN-6 in patients with pre-existing diabetic retinopathy on insulin; requires ophthalmologic monitoring in that group.", "s": "moderate" }, { "t": "Compounded and counterfeit supply", "d": "FDA has repeatedly warned about compounded \"semaglutide salts\" and counterfeit pens with incorrect content, unsafe dosing instructions, and non-sterile preparation.", "s": "high" }, { "t": "Weight regain on discontinuation", "d": "The STEP 1 extension found most lost weight returned within a year of stopping. It is a maintenance therapy, not a course of treatment.", "s": "moderate" } ], "avoid": [ "Personal or family history of medullary thyroid carcinoma or MEN2", "Prior pancreatitis (relative)", "Pregnancy and breastfeeding", "Type 1 diabetes as monotherapy", "Active gastroparesis" ], "monitoring": [ "HbA1c and fasting glucose", "Weight and body composition", "Renal function during vomiting/diarrhea", "Dilated eye exam in pre-existing retinopathy", "Lipase only if symptomatic" ], "legal": "Prescription drug. Compounded versions are permitted only under specific FDA conditions, which have narrowed as shortages resolved. Peptides sold online as \"research semaglutide\" are unapproved and unverified.", "evidenceNotes": [ "More than 15 phase 3 trials with hard clinical endpoints, not just surrogate markers.", "Cardiovascular and kidney benefits are event-driven — the strongest evidence class available." ], "tags": [ "weight loss", "diabetes", "GLP-1", "appetite", "cardiometabolic" ], "interactions": [ "Insulin and sulfonylureas — dose reduction usually required to avoid hypoglycemia", "All oral medications — delayed gastric emptying alters absorption; matters most for narrow-therapeutic-index drugs such as levothyroxine and warfarin", "Anesthesia — societies advise withholding before elective procedures because of retained gastric contents and aspiration risk", "Alcohol — compounds nausea and hypoglycemia risk" ], "confusedWith": [ { "slug": "tirzepatide", "why": "Both weekly injections for weight and glucose, and frequently swapped between. Tirzepatide adds GIP agonism and produces larger average weight loss; semaglutide has the stronger cardiovascular and kidney outcome evidence." }, { "slug": "liraglutide", "why": "Same drug class from the same manufacturer. Liraglutide is daily with roughly half the weight effect, and is now available as a generic." } ] }, { "slug": "semax", "name": "Semax", "aka": [ "ACTH (4-10) Pro-Gly-Pro", "N-acetyl semax" ], "category": "cognitive", "chemClass": "Synthetic heptapeptide analog of ACTH (4-10) with no corticotropic activity", "route": "Intranasal (primary), subcutaneous", "halfLife": "Minutes systemically; central effects outlast plasma levels", "status": "limited", "statusNote": "Registered in Russia for stroke, cognitive disorders and optic nerve conditions. Not approved in the US, EU or UK.", "evidence": 2, "summary": "A well-established medicine in Russia with essentially no Western trial replication. The pharmacology is plausible and the domestic clinical literature is substantial; the problem is that almost none of it meets the methodological standards Western regulators require.", "mechanism": "Modified ACTH fragment stripped of hormonal activity. Increases BDNF and NGF expression in the hippocampus, modulates monoaminergic and cholinergic transmission, and shows antioxidant and anti-apoptotic effects in ischemia models. The Pro-Gly-Pro tail confers resistance to peptidase degradation.", "studied": "Russian clinical trials in ischemic stroke, cognitive impairment, optic nerve atrophy and ADHD; extensive Russian preclinical neuroprotection work.", "benefits": [ { "t": "Neuroprotection in stroke models", "d": "Consistent reduction in infarct volume and improved functional recovery in animal ischemia models, supported by Russian clinical use.", "s": "preliminary" }, { "t": "BDNF upregulation", "d": "Documented increases in brain-derived neurotrophic factor expression, a plausible substrate for cognitive effects.", "s": "preliminary" }, { "t": "Reported attention and memory effects", "d": "Russian studies and extensive user reports describe improved focus and working memory; not replicated under Western trial conditions.", "s": "preliminary" }, { "t": "No corticotropic activity", "d": "Unlike ACTH itself, it does not stimulate cortisol release — an important safety feature.", "s": "moderate" }, { "t": "Good short-term tolerability", "d": "Decades of Russian clinical use without major safety signals reported.", "s": "preliminary" } ], "risks": [ { "t": "No Western regulatory review", "d": "Not evaluated by FDA or EMA. The evidence base has not been independently audited.", "s": "high" }, { "t": "Trial methodology concerns", "d": "Much of the supporting literature lacks blinding, adequate power, or placebo control by contemporary standards.", "s": "high" }, { "t": "Unknown long-term neurological effects", "d": "Chronically manipulating neurotrophin expression has no long-term human safety characterisation.", "s": "moderate" }, { "t": "Grey-market supply in the West", "d": "Purity and concentration of imported product are unverified.", "s": "high" }, { "t": "Overstimulation and irritability", "d": "Commonly reported at higher doses, along with headache and sleep disruption.", "s": "low" } ], "avoid": [ "Pregnancy", "Uncontrolled anxiety disorders", "Concurrent stimulant use without medical supervision" ], "monitoring": [ "Blood pressure", "Sleep and mood tracking" ], "legal": "Prescription medicine in Russia. Unapproved elsewhere; import for personal use occupies a legal grey area.", "evidenceNotes": [ "Large domestic literature, negligible international replication — treat both facts as real." ], "tags": [ "nootropic", "BDNF", "stroke", "intranasal", "Russia-approved" ], "confusedWith": [ { "slug": "selank", "why": "Developed at the same Russian institute and usually sold together. Semax targets cognition and neuroprotection; Selank targets anxiety. Both are registered in Russia and nowhere else." }, { "slug": "noopept", "why": "Both Russian nootropics sold as Western supplements. Semax is an intranasal ACTH fragment; noopept is an orally active dipeptide ester that FDA has ruled is not a lawful dietary ingredient." } ] }, { "slug": "sermorelin", "name": "Sermorelin", "aka": [ "GHRH (1-29)", "Geref" ], "category": "growth", "chemClass": "Truncated GHRH analog — first 29 amino acids of human GHRH", "route": "Subcutaneous, typically at night", "halfLife": "~10–20 minutes", "status": "limited", "statusNote": "Formerly FDA-approved (Geref) as a pediatric GH diagnostic; withdrawn from the US market in 2008. Now supplied through compounding pharmacies.", "evidence": 3, "summary": "The shortest biologically active fragment of GHRH. It has a legitimate history as a diagnostic agent and a large off-label life in anti-aging clinics, where the evidence is far thinner than the marketing suggests.", "mechanism": "Binds pituitary GHRH receptors, producing a brief GH pulse that mirrors natural nocturnal secretion. Because the pituitary remains in charge, somatostatin feedback caps the response — which is both its safety feature and its efficacy ceiling.", "studied": "Historic pediatric GH-deficiency diagnosis and treatment studies; small older trials in adults; extensive uncontrolled clinical use.", "benefits": [ { "t": "Physiological GH pulses", "d": "Raises GH without the flat supraphysiologic levels of injected recombinant GH, preserving feedback regulation.", "s": "moderate" }, { "t": "Documented efficacy in GH-deficient children", "d": "Older controlled data support growth velocity improvement in true deficiency.", "s": "strong" }, { "t": "Well tolerated in short-term use", "d": "Decades of clinical use with a mild side-effect profile.", "s": "moderate" }, { "t": "Low risk of pituitary suppression", "d": "Unlike exogenous GH, it does not shut down the endogenous axis.", "s": "moderate" }, { "t": "Reported sleep and recovery improvement", "d": "Commonly described by users; largely uncontrolled data, plausible given GH secretion is sleep-linked.", "s": "preliminary" } ], "risks": [ { "t": "Weak evidence for adult anti-aging use", "d": "The body-composition, energy and longevity claims made in wellness clinics have not been tested in adequate randomized trials.", "s": "moderate" }, { "t": "Very short half-life", "d": "Requires frequent dosing and produces only a transient signal.", "s": "low" }, { "t": "Glucose intolerance with sustained GH elevation", "d": "A class effect of raising the GH/IGF-1 axis.", "s": "moderate" }, { "t": "Injection-site reactions and flushing", "d": "Common and generally minor.", "s": "low" }, { "t": "Compounding variability", "d": "Potency and sterility depend entirely on the compounding pharmacy; product quality is not uniform.", "s": "moderate" }, { "t": "Contraindicated in active malignancy", "d": "Standard caution with any GH-axis stimulation.", "s": "high" } ], "avoid": [ "Active malignancy", "Pregnancy", "Untreated diabetes (relative)", "Known hypersensitivity" ], "monitoring": [ "IGF-1 as a surrogate for GH exposure", "Fasting glucose and HbA1c", "Symptoms of fluid retention or joint pain" ], "legal": "No longer an approved US drug product; lawful access is via patient-specific compounding under a prescription. FDA has scrutinised this category closely.", "evidenceNotes": [ "Strong evidence for the original pediatric diagnostic indication.", "Weak evidence for the adult wellness indications it is now mostly used for." ], "tags": [ "growth hormone", "GHRH", "anti-aging", "compounded" ], "interactions": [ "Corticosteroids — suppress the GH response", "Thyroid hormone — affects GH axis testing and response", "Insulin and antidiabetic drugs — GH elevation opposes insulin action" ] }, { "slug": "setmelanotide", "name": "Setmelanotide", "aka": [ "Imcivree" ], "category": "metabolic", "chemClass": "Melanocortin-4 receptor (MC4R) agonist — cyclic octapeptide", "route": "Subcutaneous, once daily", "halfLife": "~11 hours", "status": "approved", "statusNote": "FDA-approved for obesity due to POMC, PCSK1 or LEPR deficiency, and for Bardet-Biedl syndrome", "evidence": 5, "summary": "A precision-medicine peptide. It restores signalling in a specific broken hypothalamic pathway, and in the right genetic patient the effect is dramatic. In everyone else, it does very little — a useful reminder that peptides are not interchangeable.", "mechanism": "Agonises MC4R downstream of the leptin-melanocortin pathway. In patients whose obesity stems from an upstream defect (POMC, PCSK1, LEPR) or from ciliopathy-related signalling failure, bypassing the lesion restores satiety signalling.", "studied": "Pivotal open-label trials in POMC/LEPR deficiency and a randomized trial in Bardet-Biedl syndrome.", "benefits": [ { "t": "Large weight loss in genetically defined obesity", "d": "Most patients with POMC or LEPR deficiency achieved 10% or greater weight loss at one year, in a population previously considered untreatable.", "s": "strong" }, { "t": "Marked hunger reduction", "d": "Patient-reported hyperphagia scores fell substantially, which for these families is often more meaningful than the weight number.", "s": "strong" }, { "t": "Clear genetic selection criteria", "d": "Confirmatory genetic testing identifies responders before treatment, avoiding open-ended trials of therapy.", "s": "strong" } ], "risks": [ { "t": "Skin hyperpigmentation", "d": "Very common, because MC1R cross-activation increases melanin. New or darkening naevi need dermatologic assessment.", "s": "moderate" }, { "t": "Depression and suicidal ideation warning", "d": "Labelled warning requiring psychiatric monitoring, particularly in adolescents.", "s": "high" }, { "t": "Spontaneous penile erections", "d": "A predictable melanocortin class effect; reported in a substantial minority of male patients.", "s": "low" }, { "t": "Injection-site reactions and nausea", "d": "Common but usually manageable.", "s": "low" }, { "t": "No benefit in common polygenic obesity", "d": "It is not a general weight-loss drug and should not be sought as one.", "s": "moderate" } ], "avoid": [ "Patients without a qualifying genetic diagnosis", "Pregnancy", "Untreated significant depression (relative)" ], "monitoring": [ "Full skin examination before and during treatment", "Depression screening", "Weight and hyperphagia scores", "Growth in pediatric patients" ], "legal": "Prescription drug restricted to labelled genetic indications.", "evidenceNotes": [ "Small trials by design — the target populations are ultra-rare — but with unambiguous effect sizes." ], "tags": [ "rare disease", "melanocortin", "genetic obesity", "MC4R" ], "interactions": [ "No major pharmacokinetic interactions established", "Other melanocortin agonists — additive pigmentation and cardiovascular effects" ], "confusedWith": [ { "slug": "pt-141", "why": "Both melanocortin agonists. Setmelanotide targets MC4R for genetic obesity and is dosed daily; PT-141 targets MC3R/MC4R for sexual desire and is dosed on demand." } ] }, { "slug": "snap-8", "name": "SNAP-8 (Acetyl Octapeptide-3)", "aka": [ "Acetyl glutamyl heptapeptide-1" ], "category": "cosmetic", "chemClass": "Synthetic octapeptide — an elongated analog of Argireline", "route": "Topical", "halfLife": "Not applicable — topical", "status": "cosmetic", "statusNote": "Cosmetic ingredient. Manufacturer studies claim superiority over Argireline; independent replication is limited.", "evidence": 2, "summary": "An extended version of Argireline built on the premise that a longer SNAP-25 mimic competes more effectively in the SNARE complex. The mechanism is coherent; the evidence is thinner than for its predecessor and comes mainly from the supplier.", "mechanism": "An eight-residue extension of the acetyl hexapeptide sequence, designed for stronger competitive inhibition of SNAP-25 within the SNARE complex, reducing neurotransmitter vesicle docking and muscle contraction intensity.", "studied": "Manufacturer-sponsored topical studies reporting wrinkle-depth reduction; limited independent published work.", "benefits": [ { "t": "Reported wrinkle-depth reduction", "d": "Supplier studies report reductions of roughly 30% over 4 weeks, exceeding Argireline in the same protocols.", "s": "preliminary" }, { "t": "Good tolerability", "d": "Topical use is well tolerated with minimal irritation reported.", "s": "moderate" }, { "t": "Non-invasive alternative", "d": "No injections; usable at home.", "s": "moderate" } ], "risks": [ { "t": "Evidence base is largely manufacturer-generated", "d": "Independent peer-reviewed replication is limited.", "s": "moderate" }, { "t": "Penetration challenges", "d": "A larger peptide faces a harder time crossing the stratum corneum than the hexapeptide it extends.", "s": "moderate" }, { "t": "Effects reverse on discontinuation", "d": "Requires continued use.", "s": "low" }, { "t": "Marketing outpaces data", "d": "\"Better than Argireline\" claims rest on a narrow evidence base.", "s": "moderate" } ], "avoid": [ "Known ingredient allergy", "Irritated or broken skin" ], "monitoring": [ "None required" ], "legal": "Lawful cosmetic ingredient.", "evidenceNotes": [ "Plausible mechanism, limited independent evidence." ], "tags": [ "skin", "wrinkles", "topical", "cosmetic" ] }, { "slug": "somatropin", "name": "Somatropin (recombinant hGH)", "aka": [ "rhGH", "Genotropin", "Norditropin", "Humatrope" ], "category": "growth", "chemClass": "191-amino-acid recombinant human growth hormone — a protein, not a short peptide", "route": "Subcutaneous, daily (or weekly for long-acting analogs)", "halfLife": "~3–4 hours subcutaneously", "status": "approved", "statusNote": "FDA-approved for growth hormone deficiency, Turner syndrome, Prader-Willi syndrome, short bowel syndrome and several other indications. Distribution for anti-aging use is specifically prohibited by US federal law.", "evidence": 5, "summary": "The reference point every growth hormone secretagogue is implicitly compared against. Including it makes the comparison honest: rhGH is what actually happens when you raise growth hormone substantially, side effects included — and US law bans distributing it for anti-aging.", "mechanism": "Directly replaces growth hormone, binding the GH receptor to drive hepatic IGF-1 production, lipolysis, and protein anabolism. Unlike secretagogues it bypasses the pituitary entirely, producing sustained supraphysiological levels and suppressing endogenous secretion.", "studied": "Decades of randomized trials across pediatric and adult deficiency states; large post-marketing safety registries such as KIGS and NordiNet.", "benefits": [ { "t": "Restores growth in deficient children", "d": "Unambiguous, dose-dependent improvement in growth velocity and final adult height — the indication it was developed for.", "s": "strong" }, { "t": "Body composition in adult deficiency", "d": "Reduces fat mass and increases lean mass in genuine adult GH deficiency, with improved quality-of-life scores.", "s": "strong" }, { "t": "Bone density improvement", "d": "Increases bone mineral density over multi-year treatment in deficient adults.", "s": "moderate" }, { "t": "Multiple rare disease indications", "d": "Turner syndrome, Prader-Willi syndrome, SHOX deficiency and others, each with dedicated trial evidence.", "s": "strong" } ], "risks": [ { "t": "Distributing it for anti-aging is a federal crime in the US", "d": "GH is unusual: federal law restricts distribution to approved indications specifically, and prosecutions of anti-aging clinics have followed. This is not a grey area.", "s": "high" }, { "t": "Insulin resistance and diabetes", "d": "GH is directly counter-regulatory to insulin. New-onset type 2 diabetes is a recognised consequence of sustained therapy.", "s": "high" }, { "t": "Fluid retention, arthralgia and carpal tunnel", "d": "Dose-related and common in adults, sometimes limiting treatment.", "s": "moderate" }, { "t": "Intracranial hypertension", "d": "Uncommon but serious; presents with headache and visual change and requires prompt assessment.", "s": "high" }, { "t": "Slipped capital femoral epiphysis in children", "d": "A recognised orthopedic complication requiring surveillance during pediatric treatment.", "s": "high" }, { "t": "Malignancy caution", "d": "Contraindicated in active malignancy. Long-term registry data are broadly reassuring in deficiency, but not in healthy adults taking it to feel younger.", "s": "high" }, { "t": "Suppresses the endogenous axis", "d": "Unlike secretagogues, exogenous GH shuts down natural pituitary secretion.", "s": "moderate" }, { "t": "Counterfeit market", "d": "Widely counterfeited; seized products have contained no active ingredient or unidentified substances.", "s": "high" } ], "avoid": [ "Active malignancy", "Acute critical illness — a trial in ICU patients found increased mortality", "Proliferative diabetic retinopathy", "Closed epiphyses when used for height", "Anti-aging or performance use" ], "monitoring": [ "IGF-1 targeted to age-adjusted reference range", "Fasting glucose and HbA1c", "Thyroid function", "Fundoscopy if headache or visual symptoms", "Growth velocity and hip examination in children" ], "legal": "Prescription drug. US federal law (21 U.S.C. § 333(e)) prohibits distribution for any use other than approved indications, making anti-aging distribution a criminal offence.", "evidenceNotes": [ "One of the best-characterised hormone therapies in medicine, including a landmark trial showing harm in critical illness." ], "interactions": [ "Corticosteroids — mutually antagonistic; both doses may need adjustment", "Insulin and oral hypoglycemics — requirements typically increase", "Oral estrogen — reduces GH responsiveness, higher doses often needed", "CYP450 substrates — GH can alter clearance" ], "confusedWith": [ { "slug": "sermorelin", "why": "Sermorelin stimulates your pituitary to release its own GH and preserves feedback control. Somatropin replaces GH directly, suppresses endogenous secretion, and carries the full acromegaly-like side effect profile." }, { "slug": "cjc-1295", "why": "Marketing often implies these are equivalent. CJC-1295 has phase 1 data only; somatropin has decades of trials and a specific federal law governing its distribution." } ], "tags": [ "growth hormone", "protein", "approved", "anti-aging illegal", "reference standard" ] }, { "slug": "survodutide", "name": "Survodutide", "aka": [ "BI 456906" ], "category": "metabolic", "chemClass": "Dual glucagon / GLP-1 receptor agonist", "route": "Subcutaneous, once weekly (investigational)", "halfLife": "~6 days", "status": "trials", "statusNote": "Phase 3 (SYNCHRONIZE program) in obesity and in metabolic dysfunction-associated steatohepatitis. Not approved.", "evidence": 3, "summary": "Boehringer Ingelheim's entry in the glucagon-combination race. Its most interesting phase 2 result was not weight loss but liver histology — a majority of participants with MASH achieved improvement without worsening fibrosis, which is a harder endpoint than weight.", "mechanism": "Balanced agonism at the glucagon and GLP-1 receptors. GLP-1 suppresses appetite and improves insulin dynamics; glucagon-receptor activity increases hepatic fat oxidation and energy expenditure, which is why the liver signal is stronger than with GLP-1-only agents.", "studied": "Phase 2 obesity and MASH trials; SYNCHRONIZE phase 3 program in obesity, obesity with type 2 diabetes, and MASH.", "benefits": [ { "t": "MASH improvement in phase 2", "d": "A majority of treated participants achieved histological improvement in steatohepatitis without worsening of fibrosis — a biopsy endpoint, not a surrogate marker.", "s": "moderate" }, { "t": "Substantial weight reduction", "d": "Phase 2 showed roughly 19% mean weight loss at 46 weeks on the highest dose.", "s": "moderate" }, { "t": "Added energy expenditure", "d": "The glucagon component provides a thermogenic mechanism GLP-1-only drugs lack.", "s": "preliminary" } ], "risks": [ { "t": "Not approved anywhere", "d": "Phase 3 is ongoing; efficacy and safety conclusions remain provisional.", "s": "high" }, { "t": "High GI adverse event rate", "d": "Nausea and vomiting were common and drove discontinuations in phase 2.", "s": "moderate" }, { "t": "Heart rate increase", "d": "Observed with glucagon-receptor co-agonism across this drug class.", "s": "moderate" }, { "t": "Glycemic uncertainty", "d": "Glucagon agonism raises hepatic glucose output; the net effect depends on incretin balance and needs phase 3 confirmation.", "s": "moderate" }, { "t": "Grey-market sale", "d": "Sold illicitly as a research peptide despite having no approved use.", "s": "high" } ], "avoid": [ "Use outside a registered clinical trial" ], "monitoring": [ "Not applicable outside trials" ], "legal": "Investigational. Not approved by any regulator.", "evidenceNotes": [ "Phase 2 with a biopsy-confirmed liver endpoint — unusually rigorous for this stage.", "Phase 3 results pending." ], "interactions": [ "Insulin and sulfonylureas — hypoglycemia risk if combined", "Oral medications with narrow therapeutic windows — delayed gastric emptying alters absorption" ], "tags": [ "weight loss", "MASH", "liver", "glucagon", "investigational" ] }, { "slug": "tb-500", "name": "TB-500 / Thymosin Beta-4", "aka": [ "TB4", "Tβ4", "RGN-259 (ophthalmic TB4)" ], "category": "healing", "chemClass": "Thymosin beta-4 is a 43-amino-acid actin-sequestering protein; TB-500 is a synthetic active fragment", "route": "Subcutaneous (research); topical/ophthalmic in trials", "halfLife": "Full Tβ4 several hours; fragment not well characterised", "status": "research", "statusNote": "Full-length Tβ4 has reached phase 2/3 trials for dry eye and corneal wounds. The injectable TB-500 fragment sold to consumers is unapproved. WADA-prohibited.", "evidence": 2, "summary": "A rare case where a research peptide has real clinical trial data — but for the eye, in a topical formulation, using the full-length protein. The injectable fragment sold for tendon and muscle repair is a different product with a different evidence base, which is to say almost none.", "mechanism": "Thymosin beta-4 sequesters G-actin and regulates cytoskeletal dynamics, promoting cell migration, angiogenesis, and downregulation of inflammatory mediators. It also upregulates laminin-5 and matrix metalloproteinases involved in tissue remodelling.", "studied": "Phase 2/3 ophthalmic trials for dry eye disease and neurotrophic keratopathy; phase 2 dermal wound trials in venous stasis and epidermolysis bullosa; preclinical cardiac and CNS injury models.", "benefits": [ { "t": "Corneal wound healing evidence in humans", "d": "Ophthalmic trials of full-length Tβ4 reported improved corneal healing and dry-eye symptom scores — genuine randomized human data.", "s": "moderate" }, { "t": "Cell migration and angiogenesis", "d": "Well-characterised molecular biology supporting a role in wound repair.", "s": "moderate" }, { "t": "Anti-inflammatory and antifibrotic signals", "d": "Preclinical models show reduced scarring and inflammatory mediator expression.", "s": "preliminary" }, { "t": "Cardiac repair in animal models", "d": "Promotes epicardial progenitor activation after myocardial infarction in rodents.", "s": "preliminary" } ], "risks": [ { "t": "Injectable fragment is untested in humans", "d": "The systemic TB-500 sold online has no clinical trial support for musculoskeletal healing.", "s": "high" }, { "t": "Angiogenesis and tumour concern", "d": "Tβ4 is upregulated in several cancers and promotes tumour cell migration in laboratory models. Systemic chronic use in anyone with cancer risk is a real concern.", "s": "high" }, { "t": "No established systemic dosing or safety", "d": "Ophthalmic trials say nothing about the safety of injecting it for months.", "s": "high" }, { "t": "Unregulated supply", "d": "Research-chemical market quality problems apply.", "s": "high" }, { "t": "WADA prohibited", "d": "Athletes have been sanctioned for TB-500.", "s": "moderate" } ], "avoid": [ "Cancer history or active malignancy", "Pregnancy", "Tested athletes" ], "monitoring": [ "No validated monitoring for systemic use" ], "legal": "Ophthalmic Tβ4 remains investigational. Injectable TB-500 is unapproved and not lawfully sold for human use.", "evidenceNotes": [ "Human evidence exists but is confined to topical ophthalmic use of the full protein.", "Do not transfer that evidence to injectable fragment use — the two are not equivalent." ], "tags": [ "wound healing", "tendon", "eye", "angiogenesis", "research chemical" ], "confusedWith": [ { "slug": "bpc-157", "why": "Commonly stacked. Both lack human trial evidence for tendon and muscle repair." } ] }, { "slug": "teduglutide", "name": "Teduglutide", "aka": [ "Gattex", "Revestive" ], "category": "gut", "chemClass": "GLP-2 receptor agonist — 33-amino-acid analog resistant to DPP-4", "route": "Subcutaneous, once daily", "halfLife": "~2 hours", "status": "approved", "statusNote": "FDA-approved (2012) for short bowel syndrome in patients dependent on parenteral support.", "evidence": 5, "summary": "The intestinal counterpart to the GLP-1 drugs. Where GLP-1 suppresses appetite, GLP-2 makes the remaining bowel physically grow — taller villi, deeper crypts, more absorptive surface. For patients living on intravenous nutrition, that is the difference between a pump every night and a life.", "mechanism": "Agonises GLP-2 receptors on intestinal subepithelial myofibroblasts and enteric neurons, triggering mucosal growth: increased villus height and crypt depth, slowed gastric emptying and transit, and increased intestinal blood flow. A single alanine-to-glycine substitution blocks DPP-4 degradation, extending half-life from minutes to hours.", "studied": "STEPS phase 3 program and long-term extension studies in short bowel syndrome with intestinal failure.", "benefits": [ { "t": "Reduces parenteral nutrition dependence", "d": "A substantial proportion of patients achieved clinically meaningful reductions in weekly parenteral support volume, and some achieved complete independence from it.", "s": "strong" }, { "t": "Genuine mucosal growth", "d": "Biopsy-confirmed increases in villus height and crypt depth — structural change, not just symptom improvement.", "s": "strong" }, { "t": "Reduces infusion days per week", "d": "Fewer nights tethered to a pump, with direct quality-of-life consequences.", "s": "strong" }, { "t": "Durable with continued therapy", "d": "Extension studies show benefit maintained over years of treatment.", "s": "moderate" } ], "risks": [ { "t": "Colorectal cancer surveillance required", "d": "A drug whose entire mechanism is intestinal growth carries a theoretical neoplasia risk. Colonoscopy is required before starting and periodically thereafter, with polyp removal.", "s": "high" }, { "t": "Bowel obstruction", "d": "Mucosal growth can narrow an already compromised lumen; stoma stenosis and obstruction are recognised complications.", "s": "high" }, { "t": "Biliary and pancreatic disease", "d": "Cholecystitis, cholangitis and pancreatitis are labelled risks requiring periodic laboratory assessment.", "s": "high" }, { "t": "Fluid overload", "d": "Improved absorption can cause fluid overload if parenteral support is not reduced in step — congestive heart failure has been reported.", "s": "moderate" }, { "t": "Benefit reverses on stopping", "d": "The mucosal changes regress after discontinuation; it is indefinite therapy.", "s": "moderate" }, { "t": "Very high cost", "d": "Among the more expensive chronic therapies in gastroenterology.", "s": "low" } ], "avoid": [ "Active gastrointestinal malignancy", "Active malignancy elsewhere within the last 5 years (relative)", "Known colorectal polyps not yet removed", "Pregnancy (insufficient data)" ], "monitoring": [ "Colonoscopy before initiation, at 1 year, then every 5 years", "Bilirubin, alkaline phosphatase, lipase and amylase every 6 months", "Fluid balance and parenteral support volume", "Stoma assessment where present" ], "legal": "Prescription drug, typically prescribed through specialist intestinal failure centres.", "evidenceNotes": [ "Phase 3 trials with an objective, hard-to-game endpoint: litres of intravenous nutrition avoided." ], "interactions": [ "Oral medications — increased absorption may require dose reduction of drugs with narrow therapeutic windows", "Parenteral nutrition — must be actively reduced as absorption improves" ], "confusedWith": [ { "slug": "semaglutide", "why": "GLP-1 and GLP-2 are different hormones from the same precursor gene with opposite therapeutic aims: GLP-1 drugs reduce intake and slow the gut, GLP-2 drugs grow the gut to absorb more." } ], "tags": [ "short bowel syndrome", "GLP-2", "intestinal growth", "approved", "rare disease" ] }, { "slug": "teriparatide", "name": "Teriparatide", "aka": [ "Forteo", "PTH (1-34)" ], "category": "other", "chemClass": "Recombinant human parathyroid hormone fragment — first 34 amino acids", "route": "Subcutaneous, once daily", "halfLife": "~1 hour", "status": "approved", "statusNote": "FDA-approved for severe osteoporosis at high fracture risk. The osteosarcoma boxed warning and 2-year lifetime limit were removed in 2020–21 following long-term surveillance data.", "evidence": 5, "summary": "A peptide that genuinely builds bone rather than merely slowing its loss — the first anabolic osteoporosis therapy. It is also a clean example of pulsatile versus continuous hormone exposure producing opposite biological effects.", "mechanism": "Intermittent daily PTH receptor activation preferentially stimulates osteoblast activity over osteoclast activity, producing net bone formation. Continuous PTH elevation, as in hyperparathyroidism, does the reverse and causes bone loss. The dosing interval is the whole mechanism.", "studied": "Fracture Prevention Trial and numerous subsequent randomized trials, including head-to-head comparisons against bisphosphonates.", "benefits": [ { "t": "Reduces vertebral fractures", "d": "Roughly 65% reduction in new vertebral fractures in the pivotal trial — among the largest effects in osteoporosis therapeutics.", "s": "strong" }, { "t": "Reduces non-vertebral fractures", "d": "Approximately 53% reduction in non-vertebral fragility fractures.", "s": "strong" }, { "t": "Genuinely anabolic", "d": "Increases bone mineral density and improves trabecular microarchitecture, rather than only inhibiting resorption.", "s": "strong" }, { "t": "Superior to bisphosphonates in high-risk patients", "d": "The VERO trial showed fewer fractures than risedronate in patients with severe osteoporosis.", "s": "strong" }, { "t": "Accelerates fracture and non-union healing", "d": "Supported by smaller studies and increasingly used off-label for this purpose.", "s": "moderate" } ], "risks": [ { "t": "Historic osteosarcoma signal", "d": "Rats given high lifetime doses developed osteosarcoma. Long-term human surveillance did not confirm the risk, and the boxed warning was removed — but caution persists in patients with pre-existing bone malignancy risk.", "s": "moderate" }, { "t": "Hypercalcemia", "d": "Transient elevations are common; persistent hypercalcemia requires dose review.", "s": "moderate" }, { "t": "Orthostatic hypotension", "d": "Occurs particularly with early doses; patients are advised to inject where they can sit or lie down.", "s": "moderate" }, { "t": "Bone density loss after stopping", "d": "Gains are lost unless followed by an antiresorptive agent. Sequencing is essential, not optional.", "s": "high" }, { "t": "Nausea, leg cramps, headache", "d": "Common but usually manageable.", "s": "low" }, { "t": "Contraindicated with prior skeletal radiation", "d": "Along with Paget disease, unexplained alkaline phosphatase elevation, and bone metastases.", "s": "high" } ], "avoid": [ "Prior external beam or implant radiation to the skeleton", "Paget disease of bone", "Bone metastases or skeletal malignancy", "Pre-existing hypercalcemia", "Pregnancy" ], "monitoring": [ "Serum calcium", "Bone mineral density by DXA", "Renal function", "Plan for sequential antiresorptive therapy before stopping" ], "legal": "Prescription drug; biosimilar and generic versions are now available.", "evidenceNotes": [ "Fracture-endpoint randomized trials — the strongest evidence class in osteoporosis." ], "tags": [ "osteoporosis", "bone", "anabolic", "approved", "fracture prevention" ], "interactions": [ "Digoxin — hypercalcemia may predispose to digoxin toxicity", "Calcium and vitamin D supplements — needed for efficacy but contribute to hypercalcemia risk", "Thiazide diuretics — additive hypercalcemia", "Bisphosphonates — concurrent use may blunt the anabolic effect; sequential use after teriparatide is standard" ] }, { "slug": "tesamorelin", "name": "Tesamorelin", "aka": [ "Egrifta" ], "category": "growth", "chemClass": "Stabilised growth hormone-releasing hormone (GHRH) analog", "route": "Subcutaneous, once daily", "halfLife": "~26–38 minutes", "status": "approved", "statusNote": "FDA-approved for reduction of excess visceral abdominal fat in HIV-associated lipodystrophy", "evidence": 5, "summary": "The only GHRH-class peptide with full FDA approval. It raises endogenous growth hormone in a pulsatile, physiological pattern rather than replacing it, and has real trial data for visceral fat reduction.", "mechanism": "Binds pituitary GHRH receptors to stimulate endogenous GH secretion, preserving negative feedback and pulsatility. The resulting GH/IGF-1 rise promotes lipolysis, with a disproportionate effect on visceral adipose tissue.", "studied": "Two phase 3 trials in HIV-associated lipodystrophy; investigator-led studies in NAFLD and in HIV-associated cognitive complaints.", "benefits": [ { "t": "Selective visceral fat reduction", "d": "Roughly 15–18% reduction in visceral adipose tissue by CT over 26 weeks, without equivalent loss of subcutaneous fat.", "s": "strong" }, { "t": "Triglyceride improvement", "d": "Consistent reductions in triglycerides accompanied the visceral fat loss.", "s": "moderate" }, { "t": "Liver fat reduction", "d": "An NIH-supported randomized trial showed reduced hepatic fat and slowed fibrosis progression in people with HIV and NAFLD.", "s": "moderate" }, { "t": "Physiological GH pattern", "d": "Preserves pituitary feedback, so it does not suppress the axis the way exogenous GH does.", "s": "moderate" } ], "risks": [ { "t": "Glucose intolerance", "d": "GH is counter-regulatory to insulin; fasting glucose and HbA1c can rise, occasionally unmasking diabetes.", "s": "moderate" }, { "t": "Fluid retention, arthralgia, carpal tunnel", "d": "Classic GH-excess side effects, dose-related.", "s": "moderate" }, { "t": "Contraindicated in active malignancy", "d": "GH/IGF-1 elevation is avoided where a growth-sensitive tumour may be present.", "s": "high" }, { "t": "Benefit reverses on stopping", "d": "Visceral fat returns after discontinuation; it is chronic therapy.", "s": "moderate" }, { "t": "Injection-site reactions and hypersensitivity", "d": "Common; anaphylaxis has been reported rarely.", "s": "low" }, { "t": "Off-label anti-aging marketing", "d": "Widely promoted in wellness clinics for indications it has never been tested in.", "s": "moderate" } ], "avoid": [ "Pregnancy", "Active malignancy", "Disrupted hypothalamic-pituitary axis from surgery, radiation or trauma", "Uncontrolled diabetes (relative)" ], "monitoring": [ "Fasting glucose and HbA1c", "IGF-1", "Waist circumference or CT visceral fat", "Age-appropriate cancer screening" ], "legal": "Prescription drug; on-label use is narrow. Compounded GHRH analogs sold for anti-aging are a different regulatory situation entirely.", "evidenceNotes": [ "Two adequately powered phase 3 trials with imaging endpoints.", "Positive independent NIH-funded trial in a second indication." ], "tags": [ "visceral fat", "growth hormone", "HIV lipodystrophy", "liver fat" ], "interactions": [ "Insulin and antidiabetic drugs — glucose intolerance is a recognised effect; requirements may increase", "Corticosteroids — blunt the GH response", "CYP3A4 substrates — GH can alter clearance; relevant with antiretroviral regimens in the labelled population", "Simvastatin and ritonavir-boosted regimens — review interaction profiles in HIV patients" ] }, { "slug": "thymalin", "name": "Thymalin", "aka": [ "Thymus extract peptide complex" ], "category": "immune", "chemClass": "Polypeptide complex extracted from calf thymus — a mixture, not a single molecule", "route": "Intramuscular", "halfLife": "Not applicable — heterogeneous mixture", "status": "limited", "statusNote": "Registered in Russia as an immunomodulator. Not approved in the US, EU or UK.", "evidence": 2, "summary": "A calf thymus extract used in Russian clinical practice for decades, and heavily promoted in Western longevity circles on the strength of a long-term study reporting reduced mortality in elderly subjects. Independent replication does not exist.", "mechanism": "Proposed to restore T-lymphocyte differentiation and normalise the CD4/CD8 ratio in immunodeficient states. As an undefined extract, the active constituents are not fully characterised, which limits mechanistic reasoning.", "studied": "Russian clinical studies in immunodeficiency and post-surgical infection; a long-term gerontology cohort study reporting mortality reduction in elderly participants.", "benefits": [ { "t": "Reported immune restoration", "d": "Russian studies describe normalisation of lymphocyte subsets in immunodepressed patients.", "s": "preliminary" }, { "t": "Long-term mortality signal", "d": "A multi-year cohort study reported reduced mortality in treated elderly subjects. The study design and independence are significant caveats.", "s": "preliminary" }, { "t": "Long clinical use history", "d": "Decades of use in Russian practice without prominent safety signals reported.", "s": "preliminary" } ], "risks": [ { "t": "Undefined composition", "d": "An extract rather than a defined molecule, so batch consistency and mechanism attribution are both uncertain.", "s": "high" }, { "t": "No independent replication", "d": "The evidence base traces almost entirely to one research tradition and has not been reproduced elsewhere.", "s": "high" }, { "t": "Bovine biological source", "d": "Theoretical transmissible agent concerns and hypersensitivity risk from animal-derived protein.", "s": "moderate" }, { "t": "Autoimmune and transplant contraindications", "d": "Immune stimulation is inappropriate in autoimmune disease and after transplant.", "s": "high" }, { "t": "Unregulated in the West", "d": "Imported product has no quality assurance.", "s": "high" } ], "avoid": [ "Autoimmune disease", "Organ transplant recipients", "Pregnancy", "Known bovine protein allergy" ], "monitoring": [ "CBC with differential and lymphocyte subsets if used clinically" ], "legal": "Registered in Russia; unapproved elsewhere.", "evidenceNotes": [ "Single-tradition evidence base with extraordinary longevity claims and no external replication." ], "confusedWith": [ { "slug": "thymosin-alpha-1", "why": "Thymosin alpha-1 is a single defined 28-amino-acid peptide approved in more than 30 countries with randomized hepatitis trials behind it. Thymalin is an undefined bovine extract registered only in Russia." } ], "tags": [ "immune", "thymic", "longevity", "Russia-approved", "extract" ] }, { "slug": "thymosin-alpha-1", "name": "Thymosin Alpha-1", "aka": [ "Tα1", "Zadaxin", "thymalfasin" ], "category": "immune", "chemClass": "Naturally occurring 28-amino-acid thymic peptide", "route": "Subcutaneous", "halfLife": "~2 hours", "status": "limited", "statusNote": "Approved in more than 30 countries for hepatitis B/C and as a vaccine adjuvant. Not FDA-approved; US orphan designations exist.", "evidence": 4, "summary": "A genuine immunomodulatory drug with real approvals — just not in the United States. It has been studied in hepatitis, sepsis, cancer immunotherapy adjuvancy and severe infection, with a body of evidence far beyond the typical wellness peptide.", "mechanism": "Acts largely through Toll-like receptor signalling on dendritic cells, promoting T-cell maturation and shifting responses toward a Th1 phenotype. Increases IL-2 and interferon-gamma production and restores lymphocyte counts in immunodepleted states.", "studied": "Randomized trials in chronic hepatitis B and C, sepsis (including a large Chinese sepsis RCT), severe COVID-19 cohorts, and as an adjunct in several cancers.", "benefits": [ { "t": "Antiviral effect in chronic hepatitis B", "d": "Randomized trials support improved sustained response, particularly in combination regimens; the basis of its approvals.", "s": "strong" }, { "t": "Immune reconstitution in sepsis", "d": "Trials in septic patients showed improved lymphocyte counts and monocyte HLA-DR expression, with mortality signals that remain debated.", "s": "moderate" }, { "t": "Vaccine adjuvant activity", "d": "Improves antibody response to influenza and hepatitis B vaccination in dialysis and elderly populations.", "s": "moderate" }, { "t": "Favourable safety record", "d": "Decades of clinical use in approved markets with a mild adverse-event profile.", "s": "strong" }, { "t": "Oncology adjunct signals", "d": "Studied alongside chemotherapy in melanoma and hepatocellular carcinoma with mixed but non-trivial results.", "s": "preliminary" } ], "risks": [ { "t": "Not FDA-approved", "d": "US access is via compounding or importation; FDA has scrutinised the compounded supply of thymic peptides.", "s": "moderate" }, { "t": "Autoimmune disease flare risk", "d": "Immune stimulation is contraindicated in active autoimmune conditions and after organ transplant.", "s": "high" }, { "t": "Transplant rejection risk", "d": "Enhancing T-cell function in a transplant recipient is directly counterproductive.", "s": "high" }, { "t": "Injection-site reactions", "d": "The most common adverse event; usually mild.", "s": "low" }, { "t": "Evidence quality varies by trial region", "d": "Much of the positive data comes from trials with methodological limitations; Western regulatory reviews have not been persuaded.", "s": "moderate" } ], "avoid": [ "Solid organ transplant recipients", "Active autoimmune disease", "Pregnancy (insufficient data)", "Concurrent immunosuppressive therapy" ], "monitoring": [ "CBC with differential and lymphocyte subsets", "Liver function tests where used for hepatitis", "Autoimmune symptom review" ], "legal": "Approved outside the US. In the US it is unapproved; access routes are legally constrained.", "evidenceNotes": [ "Among the strongest evidence bases of any peptide sold in the wellness market — but with real geographic and quality caveats." ], "tags": [ "immune", "antiviral", "hepatitis", "sepsis", "thymic" ], "interactions": [ "Immunosuppressants — directly opposed mechanisms; combination is generally inappropriate", "Corticosteroids — may blunt the immunomodulatory effect" ], "confusedWith": [ { "slug": "tb-500", "why": "Different molecules despite similar names. Thymosin alpha-1 is a defined 28-residue immune peptide approved in 30+ countries; thymosin beta-4 (TB-500) is an actin-binding repair peptide that is approved nowhere." }, { "slug": "thymalin", "why": "Thymosin alpha-1 is a single defined peptide with randomized hepatitis trials. Thymalin is an undefined bovine thymus extract registered only in Russia." } ] }, { "slug": "tirzepatide", "name": "Tirzepatide", "aka": [ "Mounjaro", "Zepbound" ], "category": "metabolic", "chemClass": "Dual GIP / GLP-1 receptor agonist — 39-amino-acid acylated peptide", "route": "Subcutaneous, once weekly", "halfLife": "~5 days", "status": "approved", "statusNote": "FDA-approved for type 2 diabetes, chronic weight management, and obstructive sleep apnea in obesity", "evidence": 5, "summary": "A single molecule that activates two incretin receptors. In head-to-head and cross-trial comparison it produces the largest average weight loss of any approved pharmacotherapy, approaching the range of sleeve gastrectomy.", "mechanism": "Agonises both the GIP and GLP-1 receptors. GLP-1 activity drives satiety and glucose-dependent insulin release; the added GIP component appears to improve insulin sensitivity, adipose handling of nutrients, and may blunt GLP-1-related nausea, allowing higher effective dosing.", "studied": "SURPASS program (type 2 diabetes), SURMOUNT program (obesity, sleep apnea, heart failure), SURPASS-CVOT (cardiovascular outcomes).", "benefits": [ { "t": "Best-in-class weight reduction", "d": "SURMOUNT-1 reported roughly 21% mean body-weight reduction at 72 weeks on the 15 mg dose, with more than half of participants losing at least 20%.", "s": "strong" }, { "t": "Superior HbA1c lowering", "d": "Reductions up to about 2.4 percentage points, and superiority over semaglutide 1 mg in the head-to-head SURPASS-2 trial.", "s": "strong" }, { "t": "Treats obstructive sleep apnea", "d": "SURMOUNT-OSA showed large reductions in apnea-hypopnea index, leading to a specific FDA approval — the first drug approved for OSA.", "s": "strong" }, { "t": "Favourable body-composition split", "d": "Sub-studies using imaging suggest a relatively high proportion of fat mass in total weight lost compared with diet alone, though lean loss still occurs.", "s": "moderate" }, { "t": "Blood pressure and lipid improvement", "d": "Consistent reductions in systolic blood pressure and triglycerides across the phase 3 program.", "s": "moderate" } ], "risks": [ { "t": "Gastrointestinal side effects", "d": "Nausea, diarrhea, vomiting and constipation are dose-related and most common during escalation.", "s": "moderate" }, { "t": "Thyroid C-cell tumor boxed warning", "d": "Same rodent-derived contraindication as other incretin agonists: medullary thyroid carcinoma history or MEN2.", "s": "high" }, { "t": "Pancreatitis and gallbladder events", "d": "Uncommon but serious; rapid weight loss increases gallstone formation.", "s": "high" }, { "t": "Hypoglycemia in combination therapy", "d": "Risk rises substantially when added to sulfonylureas or insulin — those doses usually need reduction.", "s": "moderate" }, { "t": "Lean mass loss", "d": "As with all rapid weight-loss interventions, muscle is lost alongside fat without deliberate protein and resistance-training countermeasures.", "s": "moderate" }, { "t": "Anesthesia and aspiration risk", "d": "Delayed gastric emptying warrants pre-procedure planning.", "s": "moderate" }, { "t": "Counterfeit market", "d": "Regulators have seized counterfeit tirzepatide vials; grey-market \"research\" tirzepatide has no identity or sterility assurance.", "s": "high" } ], "avoid": [ "Medullary thyroid carcinoma or MEN2 history", "Pregnancy", "Severe gastroparesis", "Prior pancreatitis (relative)" ], "monitoring": [ "HbA1c, glucose", "Weight and lean mass", "Hydration and renal function", "Concomitant insulin/sulfonylurea dosing" ], "legal": "Prescription drug. FDA has stated tirzepatide is no longer in shortage, which sharply restricts lawful compounding.", "evidenceNotes": [ "Multiple phase 3 trials with active comparators, not just placebo.", "Sleep apnea approval was based on a dedicated randomized trial with objective polysomnography endpoints." ], "tags": [ "weight loss", "diabetes", "GLP-1", "GIP", "sleep apnea" ], "interactions": [ "Insulin and sulfonylureas — hypoglycemia risk rises substantially; doses typically need reducing", "Oral contraceptives — reduced effectiveness around dose escalation; a barrier method is advised for 4 weeks after each increase", "Oral medications generally — delayed gastric emptying affects absorption", "Anesthesia — pre-procedural withholding guidance applies" ], "confusedWith": [ { "slug": "retatrutide", "why": "Retatrutide adds a third receptor (glucagon) and shows larger phase 2 weight loss, but it is unapproved and has no phase 3 safety data. Tirzepatide is an approved drug; retatrutide is not." } ] }, { "slug": "vancomycin", "name": "Vancomycin", "aka": [ "Vancocin" ], "category": "antimicrobial", "chemClass": "Glycopeptide antibiotic — a heavily modified, glycosylated seven-residue peptide", "route": "Intravenous; oral for C. difficile colitis (not absorbed)", "halfLife": "~4–6 hours with normal renal function", "status": "approved", "statusNote": "FDA-approved for serious Gram-positive infections including MRSA, and orally for Clostridioides difficile infection.", "evidence": 5, "summary": "Seventy years old and still a first-line drug — the definitive answer to anyone who thinks peptide therapeutics are new. It is also the clearest example of route determining everything: intravenous vancomycin treats bloodstream infection and cannot treat C. difficile, while oral vancomycin treats C. difficile and cannot treat anything else.", "mechanism": "Binds the D-alanyl-D-alanine terminus of peptidoglycan precursors, physically blocking transglycosylation and transpeptidation and halting cell wall synthesis. Resistance arises when organisms substitute D-alanyl-D-lactate, which drops binding affinity a thousandfold.", "studied": "Seven decades of clinical use, numerous randomized trials, and randomized comparisons against fidaxomicin and metronidazole for C. difficile.", "benefits": [ { "t": "Reliable anti-MRSA activity", "d": "Long-standing first-line therapy for serious methicillin-resistant staphylococcal infection.", "s": "strong" }, { "t": "Oral therapy for C. difficile", "d": "Because it is not absorbed, oral vancomycin reaches very high colonic concentrations. Superior to metronidazole in randomized comparison and a guideline-recommended first-line agent.", "s": "strong" }, { "t": "Broad Gram-positive coverage", "d": "Active against streptococci, enterococci and Gram-positive anaerobes.", "s": "strong" }, { "t": "Inexpensive and universally available", "d": "Off-patent and stocked essentially everywhere.", "s": "strong" } ], "risks": [ { "t": "Nephrotoxicity", "d": "Dose- and exposure-related acute kidney injury, markedly increased when combined with piperacillin-tazobactam — one of the most clinically important interactions in hospital medicine.", "s": "high" }, { "t": "Requires therapeutic drug monitoring", "d": "The therapeutic window is narrow; AUC-guided dosing is now recommended over trough-only monitoring.", "s": "high" }, { "t": "Vancomycin infusion reaction", "d": "Histamine-mediated flushing of the upper body from rapid infusion. It is a rate-related reaction, not an allergy, and is prevented by slowing the infusion.", "s": "moderate" }, { "t": "Ototoxicity", "d": "Uncommon but potentially permanent, particularly with aminoglycoside co-administration.", "s": "moderate" }, { "t": "Rising MICs and treatment failure", "d": "Creeping minimum inhibitory concentrations in S. aureus are associated with worse outcomes even within the susceptible range.", "s": "moderate" }, { "t": "Slow bactericidal activity", "d": "Kills more slowly than beta-lactams; not the preferred agent for methicillin-susceptible S. aureus.", "s": "moderate" }, { "t": "DRESS and severe cutaneous reactions", "d": "Vancomycin is among the more common causes of DRESS syndrome.", "s": "high" } ], "avoid": [ "Known vancomycin hypersensitivity or prior DRESS", "Caution in pre-existing renal impairment", "Avoid combining with piperacillin-tazobactam where an alternative exists" ], "monitoring": [ "AUC-guided therapeutic drug monitoring (preferred) or trough levels", "Serum creatinine at least every 2–3 days", "Audiometry with prolonged therapy or aminoglycoside co-use", "Infusion rate — at least 1 hour per gram" ], "legal": "Prescription antibiotic.", "evidenceNotes": [ "Seven decades of use plus modern randomized comparisons in C. difficile.", "Dosing guidance has changed substantially — AUC-guided dosing superseded trough-only targets." ], "interactions": [ "Piperacillin-tazobactam — substantially increased nephrotoxicity risk", "Aminoglycosides — additive nephro- and ototoxicity", "Loop diuretics — additive ototoxicity", "NSAIDs and contrast media — additive renal risk" ], "confusedWith": [ { "slug": "daptomycin", "why": "Both treat MRSA, and both are peptides. Vancomycin works in the lung; daptomycin is inactivated by surfactant and must never be used for pneumonia." } ], "tags": [ "antibiotic", "MRSA", "glycopeptide", "C. difficile", "approved" ] }, { "slug": "vip", "name": "Vasoactive Intestinal Peptide (VIP)", "aka": [ "Aviptadil", "Zyesami" ], "category": "immune", "chemClass": "Endogenous 28-amino-acid neuropeptide", "route": "Intranasal (off-label), intravenous or inhaled (trials)", "halfLife": "~1–2 minutes intravenously", "status": "trials", "statusNote": "Aviptadil (synthetic VIP) was studied in COVID-19 respiratory failure without securing approval. Intranasal VIP is used off-label in chronic inflammatory response syndrome protocols.", "evidence": 2, "summary": "A real endogenous neuropeptide with legitimate research behind it, and a substantial off-label following in the mould-illness and CIRS communities where the supporting evidence is far weaker than the enthusiasm.", "mechanism": "Binds VPAC1 and VPAC2 receptors, producing vasodilation, bronchodilation, pulmonary surfactant production in alveolar type II cells, and broad anti-inflammatory effects including cytokine suppression and regulatory T-cell promotion.", "studied": "Randomized trials of intravenous and inhaled aviptadil in COVID-19 acute respiratory failure; small studies in sarcoidosis and pulmonary hypertension; no controlled trials of intranasal VIP for CIRS.", "benefits": [ { "t": "Potent anti-inflammatory signalling", "d": "Well-characterised suppression of pro-inflammatory cytokines and promotion of regulatory immune phenotypes.", "s": "moderate" }, { "t": "Pulmonary surfactant and bronchodilation", "d": "Direct effects on alveolar type II cells, the rationale for the respiratory failure trials.", "s": "moderate" }, { "t": "Signals in sarcoidosis", "d": "Small inhaled studies showed reduced inflammatory markers in bronchoalveolar lavage.", "s": "preliminary" }, { "t": "Anecdotal CIRS symptom benefit", "d": "Reported in uncontrolled clinical series; no randomized data.", "s": "preliminary" } ], "risks": [ { "t": "COVID-19 trials did not secure approval", "d": "Results were mixed and did not persuade regulators, despite emergency-context review.", "s": "moderate" }, { "t": "Hypotension and flushing", "d": "Direct consequence of potent vasodilation; can be significant with intravenous use.", "s": "moderate" }, { "t": "Diarrhea", "d": "VIP is the hormone responsible for the secretory diarrhea of VIPoma; this is on-target, not idiosyncratic.", "s": "moderate" }, { "t": "CIRS use is unvalidated", "d": "The condition itself lacks consensus diagnostic criteria, and the treatment lacks controlled evidence.", "s": "moderate" }, { "t": "Compounded intranasal quality varies", "d": "Formulation and sterility depend entirely on the pharmacy.", "s": "moderate" } ], "avoid": [ "Hypotension or hemodynamic instability", "Pregnancy", "Known VIPoma or carcinoid" ], "monitoring": [ "Blood pressure", "Symptom diaries where used off-label" ], "legal": "No approved VIP product in the US. Intranasal preparations are compounded.", "evidenceNotes": [ "Legitimate mechanism and real trials, but no positive definitive result." ], "tags": [ "inflammation", "lung", "CIRS", "neuropeptide" ] } ] }