Exenatide (Byetta/Bydureon) holds the distinction of being the first GLP-1 receptor agonist approved by the FDA (April 28, 2005). Its discovery from Gila monster venom opened an entirely new therapeutic class for diabetes.
Origin: From Lizard to Medicine
Exenatide is synthetic exendin-4, originally isolated from Gila monster saliva. It shares 53% similarity with human GLP-1 but resists DPP-4 breakdown, providing longer therapeutic action.
Structure
39-amino acid peptide: 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
Mechanism of Action
- Increases insulin secretion (glucose-dependent)
- Decreases glucagon secretion
- Slows gastric emptying
- Promotes satiety
Formulations
Byetta (Immediate-Release)
- FDA approved: April 2005
- Dosing: 5-10 mcg SC twice daily
Bydureon (Extended-Release)
- FDA approved: January 2012
- Dosing: 2mg SC once weekly
Historical Significance
Exenatide's 2005 approval validated the incretin approach and catalyzed a revolution in diabetes and obesity therapeutics, leading to semaglutide, tirzepatide, and others.