How incretin hormones work

Sugar eaten as food triggers much more insulin than the same amount of sugar put straight into the blood. Scientists call the difference the incretin effect, and it comes from two gut hormones: GLP-1 and GIP.

Special cells in the gut lining release these hormones as food passes. They tell the pancreas that food is on the way, so it can release insulin early.

GLP-1 signals the pancreas to release insulin, but only when blood sugar is high. Researchers call this glucose-dependent. GLP-1 also lowers glucagon, slows how fast the stomach empties, and acts on appetite centers in the brain.

Natural GLP-1 is cut apart by an enzyme called DPP-4 within about two minutes. That is why the GLP-1 drugs studied today are modified versions built to last much longer.

GIP, the second incretin, mainly boosts insulin release after meals. Unlike GLP-1, it does not lower glucagon.

Amylin is released by the pancreas together with insulin. It adds a fullness signal and slows stomach emptying. Cagrilintide is a long-acting amylin analog.

Glucagon usually raises blood sugar between meals by releasing stored energy. Researchers are also studying what activating its receptor does to energy use and liver fat, which is why retatrutide includes it.