GLP-1 (glucagon-like peptide-1) is an incretin peptide hormone released from intestinal L-cells in response to nutrient intake. Its two principal circulating active forms are GLP-1(7-37) and GLP-1(7-36)amide, both derived by post-translational processing of proglucagon.
Native GLP-1 activates the GLP-1 receptor to potentiate glucose-dependent insulin secretion from pancreatic β-cells, suppress glucagon release from α-cells, slow gastric emptying and reduce food intake through central neural circuits. Its plasma half-life is very short (~1–2 minutes) because it is cleaved by dipeptidyl peptidase-4 (DPP-4).
Long-acting synthetic GLP-1 receptor agonists such as Semaglutide overcome this pharmacokinetic constraint by combining DPP-4 resistance with albumin-binding acylation.
Understanding native GLP-1 anchors the entire pharmacology of GLP-1 receptor agonists, dual agonists and triple agonists.