Incretin effect

The incretin effect is the phenomenon — first described in the 1960s — that an oral glucose load triggers substantially more insulin secretion than the same glucose load administered intravenously to produce identical plasma glucose concentrations. The magnitude is large: in healthy adults the incretin effect accounts for approximately 50–70% of the postprandial insulin response. The effect is mediated by two intestinal incretin hormones released in response to luminal nutrients: glucagon-like peptide-1 (GLP-1, secreted by ileal and colonic L-cells) and glucose-dependent insulinotropic peptide (GIP, secreted by duodenal and jejunal K-cells). Both bind class B G-protein-coupled receptors on pancreatic β-cells and potentiate glucose-stimulated insulin secretion in a glucose-dependent manner. The incretin effect is markedly attenuated in type-2 diabetes — predominantly through reduced β-cell GIP responsiveness rather than reduced GLP-1 sensitivity — which has driven the development of stable GLP-1 receptor agonists (semaglutide, liraglutide) and dual incretin agonists (tirzepatide). The strictly glucose-dependent nature of incretin-driven insulin secretion underlies the favourable hypoglycaemia profile of incretin-mimetic therapy compared with sulphonylureas. Beyond glycaemia, incretin-mimetic effects on satiety, gastric emptying, and central appetite have produced the obesity-medication revolution of the late 2020s.