Glucose-dependent insulinotropic peptide receptor (GIPR)

The Glucose-dependent insulinotropic peptide receptor (GIPR) is a member of the class B G protein-coupled receptor family and plays a critical role in metabolic regulation [UniProt P48546]. Primarily expressed in pancreatic beta-cells, activation of GIPR by its endogenous ligand, the incretin hormone GIP, stimulates insulin secretion in a glucose-dependent manner, which is essential for postprandial glycemic control [StatPearls NBK546651]. Beyond the pancreas, GIPR is found in adipose tissue, the central nervous system, and bone, where it influences lipid metabolism, satiety, and bone remodeling [PubMed 19251046]. In pharmaceutical development, GIPR is a major therapeutic target for type 2 diabetes and obesity, exemplified by dual-agonist drugs like tirzepatide that target both GIPR and GLP-1R [PubMed 34170647]. Recent clinical research also explores GIPR antagonism in dual-modality conjugates, such as maridebart cafraglutide, to further drive weight loss and potentially improve cardiovascular outcomes [NEJM 2025;393(9)].

Other names

Gastric inhibitory polypeptide receptorGlucose-dependent insulinotropic polypeptide receptorGIP receptorIncretin receptor

Agonism of the GIP receptor stimulates insulin secretion from pancreatic beta cells in a glucose-dependent manner, improves glycemic control, and modulates energy balance through central nervous system pathways. Newer therapeutic strategies include GIPR antagonism in combination with GLP-1 receptor agonism to enhance weight loss and improve metabolic profiles.