GIP.

Glucose-dependent insulinotropic polypeptide, another incretin hormone.

GIP, glucose-dependent insulinotropic polypeptide, is the other main incretin hormone. Like GLP-1 it is released from the gut after eating and enhances glucose-dependent insulin secretion, and like GLP-1 it is broken down rapidly by DPP-4. Historically GIP was the less interesting of the two for drug development, because its insulin-releasing effect appeared blunted in type 2 diabetes and because on its own it does not reduce appetite the way GLP-1 does. Interest revived with dual agonists, molecules engineered to activate both the GLP-1 and GIP receptors, which is the design behind tirzepatide. GIP receptors are found in fat tissue and in the brain as well as the pancreas, and the combination appears to affect metabolic outcomes differently from GLP-1 activity alone. There is a genuine and unresolved scientific debate here that is worth knowing about rather than glossing over: both GIP receptor agonists and GIP receptor antagonists have been pursued as metabolic candidates, and the field does not have a settled account of why opposite approaches at the same receptor can both look promising. The point to take away is that dual agonism is not simply GLP-1 with an extra ingredient, and the two receptors are not interchangeable.