Glucagon-like peptide 1 receptor and Glucose-dependent insulinotropic polypeptide receptor (GLP-1R and GIPR)

Glucagon-like peptide 1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) are class B G protein–coupled receptors that regulate glucose metabolism and energy homeostasis. GLP-1R is primarily expressed in pancreatic beta cells, the central nervous system, and other peripheral tissues, mediating insulin secretion, inhibition of glucagon, delayed gastric emptying, and appetite suppression. GIPR, mainly found in pancreatic beta cells, also enhances glucose-dependent insulin secretion but has additional actions in adipose tissue and other metabolic organs. Both receptors are central to the ‘incretin effect’, and are valuable drug targets for type 2 diabetes and obesity. The recent development of dual agonists targeting both GLP-1R and GIPR, such as tirzepatide, leverages synergistic mechanisms for superior metabolic benefits compared to single agonists.

Other names

GLP1RGlucagon-like peptide-1 receptorGIPRGastric inhibitory polypeptide receptorGlucose-dependent insulinotropic polypeptide receptor

GLP-1R agonists: Mimic endogenous GLP-1, activate GLP-1R, increase insulin secretion, inhibit glucagon, slow gastric emptying, promote satiety. GIPR agonists: Mimic GIP, activate GIPR, enhance insulin secretion in a glucose-dependent manner. Dual agonists: Simultaneously activate both GLP-1R and GIPR for synergistic metabolic effects (improved glycemic control, weight loss).