Exenatide is a 39-amino-acid GLP-1 receptor agonist (MW ~4186.6 g/mol) originally derived from exendin-4, a peptide found in the saliva of the Gila monster (Heloderma suspectum). It was the first GLP-1 receptor agonist approved by the FDA, with Byetta (twice-daily injection) approved in April 2005 and Bydureon (once-weekly extended-release) approved in January 2012, both for type 2 diabetes. Exenatide shares approximately 53% sequence homology with human GLP-1 and is resistant to DPP-4 degradation.
Category: Metabolic / GLP-1 Agonist. Evidence rating: A (strong human clinical data).
Clinical status: FDA-approved (Byetta for T2D, 2005; Bydureon for T2D, 2012)
Exenatide binds to and activates the GLP-1 receptor on pancreatic beta cells, stimulating glucose-dependent insulin secretion. It suppresses inappropriately elevated glucagon secretion, slows gastric emptying, and reduces food intake through central appetite regulation. Unlike human GLP-1,…
Research base: 0 registered clinical trials and 1 indexed publication reference Exenatide.
Safety considerations: Common (>=5%): nausea (44% with Byetta, decreases over time), vomiting, diarrhea, dizziness, headache, jitteriness; Injection site reactions more common with Bydureon extended-release (up to 17%) including nodules at injection site; Hypoglycemia risk increased when combined with sulfonylureas or insulin.
Reviewed by the PeptideAtlas Editorial Team.
| Amino-acid sequence | H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 |
|---|---|
| Molecular weight | ~4186.6 g/mol |
| CAS number | 141758-74-9 |
| Half-life | ~2.4 hours (Byetta); ~2 weeks sustained release (Bydureon) |
| Bioavailability | ~65-75% subcutaneous |
| Production method | synthetic |
| Anti-doping status | not-listed |
| US regulatory status | FDA-approved. Byetta (exenatide immediate-release) approved April 2005. Bydureon/Bydureon BCise (exenatide extended-release) approved January 2012. Both indicated for T2D as adjunct to diet and exercise. |
Related peptides: Semaglutide, Liraglutide, Dulaglutide.
Compare: Exenatide vs Liraglutide.
Exenatide is based on exendin-4 from Gila monster venom with ~53% homology to human GLP-1, while semaglutide is a modified human GLP-1 analog with 94% homology. Semaglutide has a much longer half-life (~7 days vs 2.4 hours for Byetta), generally produces greater weight loss and HbA1c reductions, and has demonstrated cardiovascular benefit (SELECT trial). Exenatide was the first-in-class GLP-1…
Exendin-4 was discovered in Gila monster saliva by Dr. John Eng in 1992. The peptide naturally resists DPP-4 degradation, making it a practical drug candidate. Amylin Pharmaceuticals developed it as exenatide (AC2993), and it became the first GLP-1 receptor agonist to reach market in 2005.
Yes, though its market share has declined with the availability of newer GLP-1 agonists like semaglutide and dulaglutide that offer greater efficacy and more convenient dosing. Exenatide remains a valid option, particularly for patients who respond well to it or prefer its specific formulation characteristics.
An exploratory Phase II trial (Athauda et al., Lancet 2017, PMID: 28781108) showed promising effects on motor function in Parkinson disease. However, this is not an approved indication, and larger confirmatory trials are needed.
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