What it is
GIP is a 42-amino-acid hormone made in the gut. Its sequence, YAEGTFISDYSIAMDKIHQQDFVNWLLAQKGKKNDWKHNITQ, is cut from residues 52–93 of a 153-residue precursor (UniProt P09681). At 42 residues it sits two above the 40-amino-acid line that US regulation (21 CFR 600.3) uses to define a protein — a peptide by name and by everyday use, protein-sized by that one rule (see peptide vs protein).
The initials have outlived the first name. GIP was described in the 1970s as gastric inhibitory polypeptide, for slowing stomach acid; early papers from that decade already report its "insulinotropic action" in dogs (Diabetes 1975, PubMed 1193309 — animal evidence). The acid effect proved weak — UniProt still calls it a "relatively poor inhibitor of gastric acid secretion" — and the hormone was renamed glucose-dependent insulinotropic polypeptide.
How it works
GIP is one of the two incretins: hormones from the gut that make the pancreas release more insulin when glucose comes in by mouth than when the same glucose is infused into a vein. "Glucose-dependent" is the point — GIP amplifies insulin release only while blood sugar is high; in the 1993 study below, GIP levels at the lower infusion rate matched those seen after oral glucose. It acts through its own receptor, the GIP receptor, distinct from GLP-1's.
The finding that shaped the drugs
In 1993, Nauck and colleagues infused synthetic human GIP and GLP-1 into 9 people with mild type 2 diabetes and 9 matched controls, holding blood sugar high with a clamp (J Clin Invest, PubMed 8423228). Both hormones raised insulin and C-peptide, but:
| Measure | GIP | GLP-1 |
|---|---|---|
| Maximum insulin effect in type 2 diabetes vs controls | 54% lower | 71% of the controls' C-peptide rise (difference not significant) |
| Lowered glucagon | No | Yes, in both groups |
The first approved incretin drugs — exenatide, liraglutide, semaglutide — all act on the GLP-1 receptor alone. GIP came back as a drug template with dual agonists. The Mounjaro label states that tirzepatide "is based on the GIP sequence", modified with aminoisobutyric acid at positions 2 and 13, a C-terminal amide and a C20 fatty diacid at lysine 20 that binds albumin and stretches its half-life; it activates both the GIP and GLP-1 receptors. Why adding GIP-receptor activity helps when GIP itself works poorly in type 2 diabetes is a live research question — GLP1Ledger's page on the GIP and GLP-1 paradox covers that debate and the drug class. This entry stays with the hormone.
Where it stands
- Native GIP is not an approved drug; it is used in research infusion studies such as the 1993 clamp study.
- Built on GIP: tirzepatide, approved as Mounjaro and Zepbound, and the trial-stage triple agonist retatrutide.
- Research record: PubMed indexes 5,712 records under either name, 510 tagged as randomised controlled trials (2026-10-17).
Related reading
GIP's partner incretin and the hormone most drugs copied is covered through semaglutide and liraglutide; its family relative glucagon raises blood sugar rather than lowering it. The insulin-release marker the 1993 study measured is C-peptide.