Overview

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.

FDA ApprovedFDA-approved for chronic idiopathic constipation and for irritable bowel syndrome with constipation.

At a glance

Regulatory status	FDA-approved for chronic idiopathic constipation and for irritable bowel syndrome with constipation.
Drug class	Guanylate cyclase-C agonist — 16-amino-acid uroguanylin analog
Route	Oral tablet, once daily
Half-life	Minimally absorbed — acts locally
Evidence rating	4/5 Strong Evidence rating 4 out of 5: Strong Consistent human randomized trials, or approval outside the United States.
Studied in	Phase 3 trials in chronic idiopathic constipation and in IBS-C.

How it works

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.

Evidence base

Rated 4 of 5 — Strong. Consistent human randomized trials, or approval outside the United States.

Solid phase 3 evidence; the tolerability advantage over linaclotide is inferred, not demonstrated head-to-head.

Benefits & potential uses

Bars indicate how well each claim is supported: three = strong human evidence, two = moderate, one = preliminary or preclinical.

Phase 3 efficacy in both indications Strong evidence

Met primary endpoints for complete spontaneous bowel movements and for abdominal pain in IBS-C.
pH-dependent activity Moderate evidence

Activity concentrated in the proximal small intestine, the rationale for a potentially gentler effect profile.
Single dose strength for constipation Moderate evidence

No titration needed for the chronic idiopathic constipation indication.
Negligible systemic absorption Strong evidence

Like linaclotide, essentially no systemic drug interactions.

Risks, cons & cautions

Bars indicate seriousness: three = serious or common, two = moderate, one = minor.

Boxed warning: contraindicated in young children Serious

Same class warning as linaclotide — contraindicated under 6 years, and not recommended between 6 and 18, due to fatal dehydration risk in juvenile animals.
Diarrhea Moderate evidence

The dominant adverse event, though rates were somewhat lower than reported for linaclotide in separate trials.
No head-to-head comparison Moderate evidence

The claim of better tolerability than linaclotide rests on cross-trial comparison, which is not reliable evidence.
Contraindicated in obstruction Serious

Same class contraindication.
Severe dehydration risk Serious

Stop the drug if severe diarrhea develops.

Who should avoid it

Children under 6 years — boxed warning
Patients aged 6 to 18 (not recommended)
Known or suspected mechanical obstruction

If used under medical supervision, monitor

Stool frequency and consistency
Hydration status
Symptom response over 4–12 weeks

Interactions

Not exhaustive. Always have a pharmacist or physician review your full medication list — including supplements.

Minimal systemic interactions
Other laxatives — additive diarrhea risk

Commonly confused with

These mix-ups cause real harm — two products sold under one name, or two molecules whose effects run in opposite directions.

Linaclotide FDA Approved Evidence 5/5

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.

Compare side by side

Regulatory & legal status

Prescription drug.

Infographic

Plecanatide — benefits & risks at a glance Download SVG

Where to read further

We link to live literature searches rather than a frozen citation list, so you always see current results — including anything published after our last review.

IBSconstipationoral peptideapproveduroguanylin

Related peptides in Gut & Gastrointestinal

Terms used on this page

Phase 3 Trial: A Phase 3 trial is the large confirmatory study, powered for a prespecified clinical endpoint, on which a marketing application and the resulting product label are built.
Primary vs Secondary Endpoint: The primary endpoint is the single prespecified outcome a trial is powered and statistically budgeted for, while secondary endpoints are additional measures that support interpretation but cannot replace it.
Drug-Drug Interaction (DDI): A drug-drug interaction is a change in one medicine's exposure or effect caused by another, arising pharmacokinetically through absorption or metabolism, or pharmacodynamically at the effect site.
Contraindication vs Precaution: A contraindication marks a situation where a drug must not be used at all, while a precaution flags a risk that calls for caution, monitoring or a modified plan rather than avoidance.
Adverse Event (AE): An adverse event is any untoward medical occurrence in someone receiving a medicine, recorded whether or not the drug caused it, which is why an event table is not a harm table.

This page is educational information, not medical advice. It cannot account for your medical history, medications, or risk factors. Do not start, stop or change any treatment based on it. Speak to a qualified healthcare professional who knows your case.