Hypoglycaemia

Hypoglycaemia is a blood glucose low enough to threaten function. International consensus grades it in three levels rather than by one number. Level 1 is a glucose below 70 mg/dL, roughly 3.9 mmol/L. Level 2 is below 54 mg/dL, about 3.0 mmol/L, where neuroglycopenic symptoms and blunted counter-regulation become likely. Level 3, severe hypoglycaemia, is defined by the need for another person's assistance regardless of the reading. Symptoms run from autonomic warnings such as tremor and sweating to confusion, seizure and coma.

The grading matters for incretin drugs, whose insulin release is glucose-dependent: GLP-1 receptor agonists amplify secretion only while glucose is raised, so monotherapy trials report rates close to placebo. Risk appears in combination with insulin or a sulfonylurea, which supply or release insulin whatever the glucose is doing; those labels handle the interaction by reducing the companion drug rather than the incretin. Exogenous insulin and IGF-1 remain the agents that cause serious hypoglycaemia outright.

That makes hypoglycaemia a regimen question more than a drug question, which changes how a safety table reads. A rate reported on a metformin background says nothing about the same agent added to basal insulin. Severe events, being assistance-defined and usually adjudicated, are the one category comparable across studies; Level 1 counts depend heavily on how often participants were asked to measure.

The misreadings run both ways. Calling GLP-1 receptor agonists hypoglycaemia-causing ignores the glucose dependence that defines them. Continuous glucose monitors worn by people without diabetes produce interstitial readings under 70 mg/dL routinely, and a tracing dip is not an event; symptoms attributed to a low with no glucose ever measured are frequently something else.