What it is
GLP-1 is a gut hormone, and a peptide. It is not made on its own: it is cut from proglucagon, a 180-residue precursor (UniProt P01275) that yields different hormones in different tissues. In the pancreas the main product is glucagon, the hormone that raises blood sugar; in the intestine's L-cells, the precursor is cut into GLP-1, GLP-2, oxyntomodulin and glicentin.
The cut matters. The full-length piece, GLP-1(1-37), is 37 amino acids and does nothing to insulin. The active hormone is shorter, missing its first six residues:
| Form | Length | Sequence (UniProt P01275) |
|---|---|---|
| GLP-1(7-36) amide | 30 | HAEGTFTSDVSSYLEGQAAKEFIAWLVKGR-NH₂ |
| GLP-1(7-37) | 31 | HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG |
| GLP-1(9-36) amide | 28 | the inactive product left after DPP-4 removes "HA" |
A 2007 review in Physiological Reviews (Holst, PMID 17928588) describes GLP-1 as "a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon."
This entry is about the hormone. The medicines sold as "GLP-1s" are separate molecules; GLP1 Ledger's explainer on GLP-1 medicines covers the drug class, their costs and side effects.
How it was found
| Year | Finding | Source |
|---|---|---|
| 1983 | The hamster preproglucagon gene encodes glucagon and two related peptides — the first sight of GLP-1 and GLP-2 | Bell et al., Nature, PMID 6835407 |
| 1983 | The human preproglucagon gene shows the same layout | Bell et al., Nature, PMID 6877358 |
| 1987 | GLP-1(7-37) releases insulin from the perfused rat pancreas at 5 × 10⁻¹¹ M; GLP-1(1-37) does not, even at 5 × 10⁻⁷ M | Mojsov, Weir and Habener, J Clin Invest, PMID 3543057 |
| 1987 | A truncated GLP-1 isolated from pig gut releases insulin from the pig pancreas | Holst et al., FEBS Lett, PMID 3542566 |
| 1987 | Infused into 7 human volunteers at meal-like levels, GLP-1(7-36) raises insulin and lowers glucose and glucagon — "a physiological incretin in man", more powerful than GIP | Kreymann et al., Lancet, PMID 2890903 |
What it does
The Holst review lists the main actions: GLP-1 stimulates insulin secretion (it is an incretin, a gut hormone that amplifies the insulin response to food), inhibits glucagon secretion, slows stomach emptying and gut secretion — part of the "ileal brake" — and "appears to be a physiological regulator of appetite and food intake." In Kreymann's 1987 infusions it was strong enough to cause reactive low blood sugar after the infusion during a glucose load. Its partner incretin is GIP.
Why it vanishes in minutes
In 1995 Deacon, Johnsen and Holst incubated GLP-1(7-36) amide in human plasma and found it converted to GLP-1(9-36) amide with a half-life of 20.4 minutes in the test tube; inhibitors of the enzyme dipeptidyl peptidase-IV (DPP-4) blocked it completely (J Clin Endocrinol Metab, PMID 7883856). In 6 people, the inactive fragment was 53.5% of intact GLP-1 when fasting and 130.8% an hour after a meal — so after eating, there is more broken hormone than working hormone in the blood. The 2007 review adds that inactivation starts "even before the hormone has left the gut."
That fragility is the whole story of the drugs. Two routes were taken: block DPP-4 so the body's own GLP-1 lasts longer (the DPP-4 inhibitors), or build a GLP-1 receptor agonist the enzyme cannot cut — exenatide, liraglutide, dulaglutide, semaglutide, and the dual-acting tirzepatide. Each has its own entry with its own sequence and label.
Where it stands
- Native GLP-1 is not an approved medicine. The approved products are engineered analogues.
- Published record: PubMed returns 31,397 records for glucagon-like peptide 1 and 34,046 with "GLP-1" or "glucagon-like peptide-1" in the title or abstract (2026-10-20). Both counts include the drugs; this library has not separated the hormone-only literature.
Related reading
The pancreatic hormone glucagon and GLP-2 are cut from the same precursor; GIP is the other incretin; semaglutide is the best-known molecule built to imitate GLP-1.