GIP Receptor
Glucose-dependent Insulinotropic Polypeptide Receptor
The GIP receptor (GIPR) is a G-protein-coupled receptor expressed on pancreatic beta cells, adipocytes, bone, and CNS tissue. GIP is the second incretin (alongside GLP-1) and acts in a glucose-dependent fashion to amplify insulin secretion in response to a meal.
GIPR pharmacology in the obesity space is more nuanced than GLP-1: chronic GIPR agonism appears to support weight loss, but the same receptor can also promote fat storage in some contexts. The precise mechanism by which dual GLP-1 / GIP agonism (tirzepatide) outperforms GLP-1 alone is still being characterized.
Tirzepatide is the first marketed dual GLP-1 / GIP agonist; retatrutide adds glucagon-receptor activity to the same mechanism for the next-generation triple-agonist class.
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