GIP

Glucose-dependent insulinotropic peptide (GIP, formerly gastric inhibitory polypeptide) is a 42-amino-acid incretin hormone secreted by enteroendocrine K-cells of the duodenum and proximal jejunum in response to luminal carbohydrate and fat ingestion. Acting through the G-protein-coupled GIP receptor (GIPR) on pancreatic β-cells, GIP potentiates glucose-stimulated insulin secretion as part of the incretin effect, alongside GLP-1. Unlike GLP-1, GIP does not suppress glucagon release in healthy subjects and may stimulate glucagon in hypoglycaemia, providing a glucose-stabilising rather than glucose-lowering profile. GIP receptors are also expressed in adipose tissue, where they regulate lipogenesis and lipolysis, and in the central nervous system. The clinical interest in GIP was reignited by tirzepatide (Mounjaro/Zepbound), a dual GIPR/GLP-1R co-agonist whose obesity and type-2-diabetes efficacy exceeds GLP-1R monoagonists, suggesting that combined incretin stimulation has additive metabolic effects. Whether GIPR agonism, antagonism, or biased agonism contributes most to this benefit remains an open research question.