Exenatide
GLP-1 receptor agonist
Status
Approved
The first GLP-1 receptor agonist approved (FDA 2005, EMA 2006); AstraZeneca discontinued Byetta and Bydureon BCise in the US in October 2024, but an FDA-approved generic exenatide pen (Amneal, November 2024) remains on the US market and both brands are still authorized in the EU.
Evidence
Strong
Placebo-controlled phase 3 trials established glucose lowering, and the EXSCEL outcomes trial (14,752 patients) assessed cardiovascular safety.
Exenatide is a synthetic copy of exendin-4, a 39-amino-acid peptide first found in Gila monster venom. It was the first GLP-1 receptor agonist approved for type 2 diabetes, as a twice-daily injection (Byetta) and later a weekly extended-release form (Bydureon).
Structure
39 residuesPoint at a bead, or focus the chain and use the arrow keys, to name it. Pick a chemistry to highlight it.
Sequence as text
H-H-G-E-G-T-F-T-S-D-L-S-K-Q-M-E-E-E-A-V-R-L-F-I-E-W-L-K-N-G-G-P-S-S-G-A-P-P-P-S-NH2
What it is used for
- Type 2 diabetes, glycemic control (approved)
- Parkinson's disease, no benefit in phase 3 (studied)
How it works
Exenatide is a lizard peptide whose sequence partly overlaps human GLP-1 and which binds and activates the human GLP-1 receptor. It increases glucose-dependent insulin secretion, suppresses inappropriately high glucagon and slows stomach emptying, lowering fasting and post-meal glucose. It is removed mainly by kidney filtration and has a half-life of about 2.4 hours, so the immediate-release form is injected twice daily, while an extended-release formulation allows once-weekly dosing.
How strong the evidence is
Strong
Placebo-controlled label trials showed HbA1c reductions when exenatide was added to metformin, a sulfonylurea or both. EXSCEL randomized 14,752 people with type 2 diabetes to once-weekly exenatide or placebo for a median 3.2 years: major cardiovascular events occurred in 11.4% versus 12.2%, confirming safety (non-inferiority) but not proving benefit (P=0.06 for superiority). In Parkinson's disease, a 62-patient trial (2017) hinted at a motor benefit, but the 194-patient phase 3 Exenatide-PD3 trial (2025) found no disease-modifying effect at 96 weeks.
Risks and side effects
- Nausea, vomiting and diarrhea
- Acute pancreatitis and acute gallbladder disease
- Acute kidney injury from dehydration; not recommended in severe kidney impairment
- Hypoglycemia with sulfonylureas or insulin
- Drug-induced thrombocytopenia (low platelets) and antibody formation (immunogenicity)
Label dosing
Label (Byetta): 5 mcg injected twice daily within 60 minutes before the morning and evening meals, increased to 10 mcg twice daily after one month if needed.
Regulatory status
| Region | Year | Approved for |
|---|---|---|
| USFDA | 2005Withdrawn 2024 | Type 2 diabetes (twice-daily injection) |
| USFDA | 2012Withdrawn 2024 | Type 2 diabetes (once-weekly extended-release; Bydureon BCise from 2017) |
| USFDA | 2024 | Type 2 diabetes (generic twice-daily exenatide pen from Amneal, referencing Byetta) |
| EUEMA | 2006 | Type 2 diabetes |
| EUEMA | 2011 | Type 2 diabetes |
Status by country
Trials of Exenatide to watch
Exenatide for smoking cessation(opens the source in a new tab)
Exenatide for Smoking Cessation and Prevention of Weight Gain
Timeline
2026
2025
2024
- SafetyEMA safety committee finds no causal link between GLP-1 drugs and suicidal thoughts
- Approved, US (FDA)Type 2 diabetes (generic twice-daily exenatide pen from Amneal, referencing Byetta)
- Withdrawn, US (FDA)Type 2 diabetes (twice-daily injection)
- Withdrawn, US (FDA)Type 2 diabetes (once-weekly extended-release; Bydureon BCise from 2017)
2012
- Approved, US (FDA)Type 2 diabetes (once-weekly extended-release; Bydureon BCise from 2017)
2011
- Approved, EU (EMA)Type 2 diabetes
2006
- Approved, EU (EMA)Type 2 diabetes
2005
- Approved, US (FDA)Type 2 diabetes (twice-daily injection)
Sources
- 01Byetta (exenatide) injection: prescribing information(opens the source in a new tab)
- 02Exenatide (D04121): sequence and structure entry(opens the source in a new tab)
- 03Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom(opens the source in a new tab)
- 04Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes (EXSCEL)(opens the source in a new tab)
- 05Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial(opens the source in a new tab)
- 06Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease (Exenatide-PD3)(opens the source in a new tab)
- 07Drugs@FDA: Byetta (NDA 021773), marketing status discontinued(opens the source in a new tab)
- 08Discontinuation of Bydureon BCise and Byetta(opens the source in a new tab)
- 09Amneal receives U.S. FDA approval of exenatide, its first generic injectable GLP-1 agonist(opens the source in a new tab)
- 10Byetta: EPAR (European public assessment report)(opens the source in a new tab)
- 11Bydureon: EPAR (European public assessment report)(opens the source in a new tab)
- 12Drugs@FDA: Exenatide (ANDA 206697, Amneal)(opens the source in a new tab)
- 13NHS Circular MSAN (2025) 48: Medicine Supply Alert Notice, Exenatide (Bydureon BCise) 2mg/0.85ml prolonged-release suspension for injection pre-filled pen(opens the source in a new tab)
- 14BYETTA 10 exenatide 10 micrograms/40 microlitres (2.4mL in total) solution for injection multidose cartridge Cancelled under Section 30(1)(c) of the Act(opens the source in a new tab)
- 15Drug Product Database: Byetta (DIN 02361817)(opens the source in a new tab)
Educational information, not medical advice. Talk to a licensed clinician before starting, stopping or changing any medicine.