Incretin

Incretins are intestinal hormones that amplify insulin release in response to glucose when food arrives by the oral route. The name derives from the incretin effect: glucose taken by mouth elicits a markedly larger insulin output than glucose given into a vein at a rate adjusted to produce an identical blood glucose profile. In healthy people, roughly one half up to two-thirds of post-meal insulin can be attributed to this gut-derived boost.

GLP-1 and GIP

In humans, only two hormones fulfil the definition. GIP comes from K-cells in the duodenum; GLP-1 comes from L-cells located further down the gut. Each is a ligand of a class B GPCR, each enhances insulin secretion only while glucose is raised — a glucose-dependence that explains much of the field’s appeal — and dipeptidyl peptidase-4 inactivates each of them within minutes by clipping after the alanine in the second slot.

Beating the DPP-4 clock

All engineered analogs in this class are designed to outrun that DPP-4 cleavage. Swapping the vulnerable residue for Aib or a D-amino acid, plus a lipid side chain that binds albumin, stretches the half-life from minutes out to days. When picking a comparator, start by clarifying which incretin receptor or receptors the compound engages, and how potently relative to each other.

Related terms

See also amylin, the dual agonist entry and GLP-1 receptor agonists. Our catalogue groups these compounds in the incretin section and the pathway hub for GLP-1.