GLP-1

Glucagon-like peptide-1 (GLP-1) is an incretin hormone derived from post-translational processing of the proglucagon gene in intestinal L-cells of the distal small bowel and colon. Two biologically active forms exist — GLP-1(7-37) and GLP-1(7-36)amide, the latter representing the predominant circulating species. Secretion is triggered by luminal nutrients (carbohydrate, fat, protein) and amplified by neural and hormonal signals. Active GLP-1 binds the class B G-protein-coupled GLP-1 receptor on pancreatic β-cells, where it potentiates glucose-stimulated insulin secretion in a strictly glucose-dependent manner (limiting hypoglycaemia risk), and on pancreatic α-cells where it suppresses glucagon release. Central GLP-1R activation in the hypothalamus and area postrema drives appetite suppression and satiety. Native GLP-1 has a plasma half-life of approximately two minutes due to rapid degradation by dipeptidyl peptidase-4 (DPP-4) cleaving the N-terminal His-Ala bond. Stable peptide and small-molecule GLP-1R agonists — exenatide, liraglutide, dulaglutide, semaglutide, oral semaglutide — have transformed type-2 diabetes and obesity management. Dual GLP-1R/GIPR agonists (tirzepatide) and triple GLP-1R/GIPR/glucagon-R agonists (retatrutide) extend the class. GLP-1 receptor agonism is mechanistically distinct from healing peptides and from GH-axis secretagogues but is increasingly relevant to the broader peptide research field.