What it is
"Incretin" is the name of a job: a hormone made in the gut, released after eating, that makes the pancreas release more insulin than the meal's blood sugar alone would. Two hormones do that job in people, and both are peptides:
| Incretin | Length | Precursor | Entry |
|---|---|---|---|
| GIP (glucose-dependent insulinotropic polypeptide) | 42 amino acids (UniProt P09681) | residues 52–93 of a 153-residue precursor | GIP |
| GLP-1 (glucagon-like peptide-1) | 30 or 31 amino acids in its active forms (UniProt P01275) | proglucagon, cut in the intestinal L-cells | GLP-1 |
Their sequences open the same way — Tyr-Ala-Glu-Gly-Thr-Phe in GIP, His-Ala-Glu-Gly-Thr-Phe in GLP-1(7-36) amide (our reading of UniProt) — and both act only when blood glucose is raised, which is what "glucose-dependent" in GIP's name means.
How the incretin effect was found and measured
The question is simple: does swallowed sugar release more insulin than the same rise in blood sugar delivered by vein? In 1964 two groups compared the routes — McIntyre, Holdsworth and Turner in The Lancet (PMID 14149200) and Elrick and colleagues (PMID 14228531) — the comparison the incretin effect is defined by.
The careful version came in 1986 from Nauck, Creutzfeldt and colleagues. They gave oral glucose, then copied each person's blood-glucose curve with an intravenous "isoglycaemic" infusion and compared the insulin:
| Study | People | Incretin share of the insulin response |
|---|---|---|
| Nauck et al. 1986, J Clin Endocrinol Metab (PMID 3522621) | 6 healthy young adults, 25 / 50 / 100 g glucose | 85.6% / 74.9% / 93.0% |
| Nauck et al. 1986, Diabetologia (PMID 3514343) | 8 healthy controls | 72.8% |
| same study | 14 people with type 2 diabetes | 36.0% |
Two findings came out of it: the effect grows with the amount swallowed, and in type 2 diabetes it is roughly halved. The same papers report a smaller share when C-peptide — a cleaner measure of insulin output — is used instead of insulin itself (27.6–62.9% in the first study), so the exact percentage depends on what is measured.
Why GLP-1, not GIP, became the drug
In 1993 Nauck, Creutzfeldt and colleagues at Göttingen infused each hormone into 9 people with type 2 diabetes and 9 matched controls under a glucose clamp (Nauck et al., J Clin Invest, PMID 8423228). GIP's maximum insulin effect was 54% lower in diabetes; GLP-1(7-36) amide still reached 71% of the controls' response, and lowered glucagon, which GIP did not. The hormone that still worked in the disease was the one to build on.
Why the natural hormones cannot be the medicine
The body clears its own incretins fast. The enzyme dipeptidyl peptidase-4 (DPP-4) clips the first two residues off GLP-1, turning GLP-1(7-36) amide into inactive GLP-1(9-36) amide — in human plasma with a half-life of 20.4 minutes in vitro (Deacon, Johnsen and Holst 1995, PMID 7883856). Every incretin drug answers that problem in one of two ways:
- Make an analogue DPP-4 cannot cut — the GLP-1 receptor agonists such as semaglutide, liraglutide and exenatide, and tirzepatide, the dual GIP and GLP-1 agonist, which is built on GIP's sequence.
- Block DPP-4 so the body's own GIP and GLP-1 last longer — the DPP-4 inhibitor tablets, which are small molecules, not peptides.
This library covers the molecules. What the drugs do for weight and diabetes, their side effects and cost belong to GLP1 Ledger's guide to what a GLP-1 is and its page on GIP and GLP-1 together.
Where it stands
- Neither native incretin is an approved drug; the approved incretin-based therapies are engineered analogues and DPP-4 inhibitors.
- Research record: PubMed indexes 3,047 records under the MeSH heading Incretins and 9,130 mentioning incretin* anywhere; ClinicalTrials.gov returns 345 studies for "incretin" as an intervention (2026-10-26).
Related reading
GLP-1 is cut from a precursor it shares with glucagon. The connecting peptide that measured insulin output in the 1986 studies has its own entry: C-peptide. Another gut hormone with a meal-time role is cholecystokinin.