Hypoglycaemia
Abnormally low blood sugar (generally below 70 mg/dL or 3.9 mmol/L), which can cause shakiness, confusion, seizures, and loss of consciousness. GLP-1 receptor agonists have low hypoglycaemia risk because they stimulate insulin secretion only when glucose is elevated (glucose-dependent mechanism).
Technical Context
Hypoglycaemia classification (ADA/EASD): Level 1 (glucose <70 mg/dL/3.9 mmol/L — alert value requiring treatment), Level 2 (glucose <54 mg/dL/3.0 mmol/L — clinically significant, associated with cognitive impairment), Level 3 (severe — requiring assistance from another person regardless of glucose level). GLP-1 RA monotherapy carries very low hypoglycaemia risk because insulin secretion is glucose-dependent — the GLP-1R-mediated cAMP/PKA signalling in beta cells requires concurrent glucose-mediated depolarisation (closure of KATP channels by ATP generated from glucose metabolism) for insulin granule exocytosis. When combined with sulfonylureas or insulin, hypoglycaemia risk increases because those agents stimulate insulin release independently of glucose. Clinical guidelines recommend reducing sulfonylurea or insulin doses when adding a GLP-1 RA.