FDA approves Byetta, the first GLP-1 receptor agonist
Byetta (exenatide), approved in April 2005 as the first GLP-1 receptor agonist, was discontinued by AstraZeneca on Oct. 25, 2024, leaving newer drugs like Ozempic and Mounjaro as the class's mainstays [2].
In April 2005, the FDA approved Byetta (exenatide) under new drug application 021773 — a twice-daily injection for type 2 diabetes and the first GLP-1 receptor agonist ever cleared in the United States. The active ingredient was a synthetic version of a peptide first identified in Gila monster venom. That approval opened a drug class that now includes semaglutide (Ozempic, Wegovy, Rybelsus) and tirzepatide (Mounjaro, Zepbound).
Two decades later, the original drug is gone from US pharmacies. AstraZeneca notified the FDA that it discontinued Byetta on Oct. 25, 2024, and discontinued the long-acting exenatide product Bydureon BCise on Oct. 28, 2024 [2]. UnitedHealthcare told providers about the discontinuations in a December 2024 notice and listed "preferred covered alternatives" so patients with its plans would keep access to a covered GLP-1 product for diabetes [2].
What replaced it
UnitedHealthcare's notice named the GLP-1 products it considered currently available to treat diabetes: Mounjaro, Ozempic, Rybelsus, Trulicity and liraglutide (the Victoza authorized generic) [2]. For its commercial plans, the insurer listed all five as preferred; for its Individual Exchange and ACA Marketplace plans, it listed Mounjaro, Ozempic, Rybelsus and Trulicity [2]. Community Plan and Medicare Advantage or Part D members were pointed to state-specific drug lists or plan-specific coverage tools [2].
It is worth being clear about what a discontinuation is and is not. The sources here say AstraZeneca discontinued the two exenatide products; they do not give a reason, and they do not describe any safety action by the FDA [2].
When a company stops selling a drug, the paperwork can follow later. The FDA regularly withdraws approval of applications after manufacturers tell the agency in writing that products are no longer marketed and ask that the approvals be withdrawn. In one such notice published Aug. 4, 2025, the agency withdrew approval of 39 new drug applications from multiple applicants, effective Sept. 3, 2025 [1]. The agency noted that applicants waived their right to a hearing by making the request, and that withdrawal under 21 CFR 314.150(c) is "without prejudice to refiling" [1]. The portion of that notice available here does not list exenatide, so whether NDA 021773 has been formally withdrawn is not established by these sources.
Why it matters for patients
Most people taking a GLP-1 today have never used exenatide, but the 2005 approval is the reason the category exists at all. It established that a peptide mimicking the gut hormone GLP-1 could be given as an injection to lower blood sugar in type 2 diabetes — the regulatory and scientific foundation that later once-weekly and dual-action drugs were built on.
The practical consequence of the 2024 discontinuations is narrower. Anyone still using Byetta or Bydureon BCise has had to move to a different product, and insurers have been steering those changes through formulary lists rather than letting patients choose freely [2]. Coverage depends heavily on plan type: the drugs UnitedHealthcare listed as preferred differ between commercial plans and Marketplace plans, and Medicare and Medicaid members were told to check plan-specific tools [2]. Those lists were accurate as of the December 2024 notice and can change.
The broader lesson is that being first does not mean being permanent. A drug can leave the market for commercial reasons while the class it launched keeps growing. These sources do not say how many US patients were using exenatide when it was pulled, nor whether any generic or alternative exenatide product remains available.
What happens next
- Oct. 25, 2024: Byetta discontinued; Oct. 28, 2024: Bydureon BCise discontinued [2].
- Dec. 19, 2024: UnitedHealthcare publishes preferred GLP-1 alternatives for affected members [2].
- Aug. 4, 2025: FDA publishes withdrawal of approval for 39 NDAs (Docket No. FDA-2025-N-2422), with withdrawal effective Sept. 3, 2025 [1].
- Oct. 3, 2025: FDA publishes a correction to that notice [1].
Whether exenatide's original application is formally withdrawn, and whether any manufacturer refiles, is not addressed in the available sources.
Sources
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