GIP (glucose-dependent insulinotropic polypeptide)

Glucose-dependent insulinotropic polypeptide is the other major incretin hormone, released from the upper small intestine after a meal. Like GLP-1 it increases insulin secretion when glucose is high, but it acts on a different receptor and has distinct effects on fat tissue and on glucagon. For years it was considered the less interesting incretin because its insulin effect is blunted in type 2 diabetes.

That view changed with tirzepatide, a single molecule engineered to activate both the GIP and GLP-1 receptors. In head-to-head trials the dual agonist produced larger effects on glucose and body weight than the GLP-1 agonist semaglutide, and the mechanism by which GIP contributes is still under active study. Retatrutide keeps the GIP arm and adds glucagon-receptor activity on top.

GIP is not available as a research compound on its own here; its relevance is as one arm of the dual and triple agonists. The retatrutide versus tirzepatide comparison lays out the receptor coverage of the three incretin compounds side by side.