GIP

GIP (glucose-dependent insulinotropic polypeptide) is a second gut hormone, released after eating, that — like GLP-1 — helps the pancreas release insulin in response to food. For years it was the less-famous of the two incretin hormones. Then tirzepatide made it a headline.

Why it matters now

Tirzepatide (the molecule in Zepbound and Mounjaro) is a dual agonist: it activates both the GLP-1 receptor and the GIP receptor. Pure GLP-1 drugs like semaglutide hit only the first. The leading theory for why tirzepatide produced larger average weight loss in its trials — about 21% at the top dose in SURMOUNT-1, versus about 15% for semaglutide in STEP 1 — is that engaging GIP as well adds to the appetite and metabolic effects.

The honest caveat

The exact contribution of GIP is still an active research question — the science of why dual agonism works better isn’t fully settled, and “more receptors” isn’t automatically “better for everyone.” What’s settled is the outcome data. For someone choosing between medications, GIP is the one-word reason tirzepatide and semaglutide aren’t the same drug, and the reason response can differ between them person to person.

The next generation goes further: retatrutide, in trials, adds a third target (glucagon) — a triple agonist.