Exenatide
Exenatide is an approved GLP-1 therapy for type 2 diabetes and was the first drug in its class. It is a synthetic form of exendin-4, a peptide originally identified in the saliva of the Gila monster, that shares partial sequence homology with human GLP-1. Immediate-release (Byetta) and once-weekly extended-release (Bydureon) formulations lower HbA1c and body weight; the EXSCEL cardiovascular outcomes trial found it did not increase cardiovascular risk. In recent years the originator has discontinued supply of some exenatide formulations in certain markets.
Mechanism
In plain terms, exenatide mimics a gut-hormone-like peptide that lowers blood sugar and reduces appetite. Technically, it is a synthetic exendin-4 that agonizes the GLP-1 receptor while resisting degradation by the enzyme DPP-4, stimulating glucose-dependent insulin secretion, suppressing glucagon, slowing gastric emptying, and promoting satiety. The extended-release formulation encapsulates exenatide in biodegradable microspheres to allow once-weekly dosing.
Regulatory Status by Region
- United States (FDA)Approved. Byetta (exenatide twice daily) for type 2 diabetes (2005), the first GLP-1 receptor agonist approved, and Bydureon (extended-release, once weekly) (2012).
- Australia (TGA)Registered on the ARTG for type 2 diabetes, available on prescription.
- European Union (EMA)Authorized: Byetta (2006) and Bydureon (2011) for type 2 diabetes.
- WADANot prohibited. GLP-1 receptor agonists are not on the WADA Prohibited List and are not banned substances; the class is tracked under WADA's monitoring program rather than prohibited.
Key Studies
- Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes (EXSCEL; Holman et al.) (N Engl J Med 2017;377:1228-1239; DOI 10.1056/NEJMoa1612917; PMID 28910237)
- Exenatide once weekly versus twice daily for the treatment of type 2 diabetes (DURATION-1; Drucker et al.) (Lancet 2008;372:1240-1250)