GLP-1 (Glucagon-Like Peptide-1) is a 30-amino acid incretin hormone secreted by intestinal L-cells in response to food intake. It is the endogenous peptide behind the revolutionary class of GLP-1 receptor agonist drugs including semaglutide (Ozempic/Wegovy), tirzepatide (Mounjaro/Zepbound), and liraglutide (Saxenda). Native GLP-1 has a half-life of only 2-3 minutes due to rapid degradation by DPP-4 enzymes. All approved GLP-1 receptor agonist drugs are engineered analogs with extended half-lives. GLP-1-based therapies represent one of the most significant therapeutic advances in diabetes and obesity treatment in decades.
Category: Metabolic / Weight Loss. Evidence rating: A (strong human clinical data).
Clinical status: Endogenous hormone. Multiple analogs FDA-approved: semaglutide, liraglutide, exenatide, dulaglutide, tirzepatide (dual GIP/GLP-1).
GLP-1 binds to the GLP-1 receptor (GLP-1R), a class B G-protein coupled receptor expressed in pancreatic beta cells, the hypothalamus, brainstem, heart, kidney, and GI tract. In beta cells, GLP-1R activation stimulates glucose-dependent insulin secretion via cAMP/PKA and Epac2 pathways. It…
Safety considerations: Native GLP-1 has minimal safety concerns due to ultra-short half-life; GLP-1 receptor agonist class effects: nausea (20-44%), vomiting, diarrhea, constipation; GI side effects are dose-dependent and typically improve with dose titration.
Reviewed by the PeptideAtlas Editorial Team.
| Amino-acid sequence | HAEGTFTSDVSSYLEGQAAKEFIAWLVKGR-NH2 |
|---|---|
| Molecular weight | ~3298 g/mol |
| Half-life | 2-3 minutes (native); 7 days (semaglutide); 5 days (tirzepatide) |
| Production method | recombinant |
| Anti-doping status | not-listed |
| US regulatory status | Multiple GLP-1 RAs FDA-approved: semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Victoza, Saxenda), tirzepatide (Mounjaro, Zepbound), dulaglutide (Trulicity), exenatide (Byetta, Bydureon). |
GLP-1 is the natural hormone your body makes, with a half-life of 2-3 minutes. Semaglutide is a synthetic analog engineered to resist DPP-4 degradation and bind albumin, extending the half-life to ~7 days. They both act on the same GLP-1 receptor.
Technically yes, but it would be therapeutically useless. Native GLP-1 is degraded by DPP-4 within minutes. All approved GLP-1 therapies use engineered analogs with extended half-lives.
GLP-1 receptor activation suppresses appetite through both central (hypothalamic) and peripheral (gastric emptying delay) mechanisms. Long-acting analogs maintain this suppression 24/7, producing sustained caloric deficit.
Yes. Oral semaglutide (Rybelsus) is approved, and oral non-peptide GLP-1 RAs like orforglipron and danuglipron are in Phase 3 trials.
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