Approved GLP-1 medicine

Exenatide

Sold as Byetta, Bydureon BCise, Bydureon. Also called Exendin-4 (synthetic), Exendin 4, AC2993, LY2148568, Exenatide once weekly (extended-release form).

Exenatide is a lab-made copy of a hormone first found in the saliva of the Gila monster, a large lizard. It acts on the same receptor as the gut hormone GLP-1: it helps the pancreas release insulin when blood sugar is high and slows the stomach. It was approved in the US in 2005 for type 2 diabetes.

How strong is the evidence?

AnecdoteAnimalsHuman trialsApproved

Approved. Approved by a major regulator after large trials.Approved on the basis of phase 3 programmes in type 2 diabetes: placebo-controlled trials of the twice-daily form added to oral drugs (label section 14), DURATION-1 (once-weekly form gave a larger HbA1c fall than twice-daily, -1.9% vs -1.5%), and DURATION-6 (once-weekly exenatide failed non-inferiority against once-daily liraglutide, HbA1c -1.28% vs -1.48%). EXSCEL, a large cardiovascular outcomes trial, found no significant difference in major cardiovascular events (HR 0.91, 95% CI 0.83 to 1.00). Use in Parkinson's disease is unapproved: the UK phase 3 Exenatide-PD3 trial (194 people) found no benefit on motor scores at 96 weeks, and in June 2026 The Lancet published an Expression of Concern about that paper.

Last verified 2026-09-29 · how we verify

Experimental structure

Experimental structure · cryo-EM 3.7 Å · PDB 7LLL (2022)RCSB entry ↗

Exendin-4, the 39-residue peptide whose synthetic form is exenatide (the deposited sequence matches exenatide). Lower resolution (3.7 Å) than the other complexes. Nanobody Nb35 (chain N) omitted. Structure from Deganutti et al., Nat Commun 2022. Colours are ours, not the molecule's.

Acts on: GLP-1 receptor
Taken as: Subcutaneous injection. The original form (Byetta) is given twice a day before meals from a prefilled pen; extended-release forms (Bydureon, Bydureon BCise) are given once a week.
Half-life: About 2.4 hours (terminal half-life of the twice-daily immediate-release form)[src]
First US approval: Byetta was first approved by FDA on 28 April 2005 for type 2 diabetes; the once-weekly Bydureon followed on 27 January 2012 and Bydureon BCise on 20 October 2017.[src]
Structure: Synthetic 39-amino-acid peptide amide, molecular weight 4186.6 daltons, originally identified in the lizard Heloderma suspectum.[src]
EU authorisation: Byetta was authorised in the European Union on 20 November 2006; the EMA lists AstraZeneca AB as marketing authorisation holder and the medicine as authorised.[src]

Inside the body

What Exenatide does, step by step

Watch the 3D journey →

01Skin
Absorbed from under the skin
The drug is injected just under the skin and slowly moves into the blood. The twice-daily form peaks in the blood after about two hours.
For experts
After subcutaneous administration in people with type 2 diabetes, exenatide reaches a median peak plasma concentration at 2.1 hours, with similar exposure from abdomen, thigh or upper arm. The extended-release forms embed exenatide in PLGA microspheres, so plasma levels rise gradually over weeks (up to about week 10 for Bydureon BCise) and fall below quantifiable limits about 10 weeks after stopping.[src][src]
02Bloodstream
Lasts longer than the natural hormone
In a study in pigs (animal data), natural GLP-1 was broken down within minutes, while exendin-4 (the lizard version) lasted about ten times longer. In people, exenatide stays in the blood for hours.
For experts
Exendin-4 has Gly at position 2 where human GLP-1 has Ala, and is less prone to enzymatic degradation than GLP-1. In anaesthetised pigs (animal data) exendin-4 had a half-life of about 22 minutes versus about 2 minutes for GLP-1, and its only organ extraction was renal. In people the terminal half-life of the immediate-release form is 2.4 hours.[src][src]
03Pancreas
Prompts insulin release when sugar is high
Exenatide switches on GLP-1 receptors on the pancreas cells that make insulin. They release insulin mainly when blood sugar is high, and the effect fades as sugar comes down.
For experts
Exenatide binds and activates the human GLP-1 receptor, raising cAMP-linked signalling and glucose-dependent insulin synthesis and secretion in beta cells. In humans with type 2 diabetes it restored first-phase insulin response to an intravenous glucose bolus and increased second-phase secretion versus saline; insulin release is predominantly in the presence of elevated glucose, and the normal glucagon response to hypoglycaemia is not impaired.[src]
04Liver
Less sugar released by the liver
Another pancreas hormone, glucagon, tells the liver to release sugar. Exenatide turns glucagon down when blood sugar is high, so the liver adds less sugar to the blood.
For experts
In type 2 diabetes exenatide moderates glucagon secretion and lowers serum glucagon during hyperglycaemia. The label attributes lower glucagon concentrations to decreased hepatic glucose output and decreased insulin demand.[src]
05Stomach
Slows the stomach
Food leaves the stomach more slowly, so sugar from a meal enters the blood more gradually.
For experts
Exenatide slows gastric emptying, reducing the rate at which meal-derived glucose appears in the circulation. The label also notes that exenatide may affect absorption of orally administered medicines.[src]
06Brain
Eating less
Studies in animals and in people show exenatide reduces how much they eat. In trials, people lost only a small amount of weight on average.
For experts
The label states that exenatide reduces food intake in both animals and humans; it does not describe the neural pathway, so the central mechanism is not established by these sources. In the 24-week placebo-controlled monotherapy trial, the mean weight change was -2.9 kg with the higher studied dose versus -1.5 kg with placebo (difference -1.5 kg, 95% CI -2.5 to -0.4). Exenatide is not approved for weight management.[src]
07Kidneys
Filtered out by the kidneys
The kidneys filter exenatide out of the blood, and it is then broken into pieces. Because of this, it is not recommended for people with severe kidney disease.
For experts
Nonclinical studies show exenatide is eliminated predominantly by glomerular filtration followed by proteolytic degradation; mean apparent clearance in humans is 9.1 L/h and apparent volume of distribution 28.3 L. In pigs (animal data) renal extraction of exendin-4 was accounted for by glomerular filtration alone.[src][src]

For experts

The detail

Exenatide is the synthetic form of exendin-4, a 39-residue peptide amide (C184H282N50O60S, 4186.6 Da) first isolated from Heloderma suspectum venom. Its sequence only partly overlaps human GLP-1; it binds and activates the human GLP-1 receptor, enhancing glucose-dependent insulin secretion, suppressing inappropriately high glucagon and slowing gastric emptying. It carries no fatty-acid chain: it is less prone to enzymatic degradation than native GLP-1 and, according to nonclinical studies, is eliminated mainly by glomerular filtration, giving a terminal half-life of about 2.4 hours (median Tmax 2.1 hours) for the twice-daily immediate-release form, Byetta. Extended-release once-weekly forms (Bydureon, Bydureon BCise) use poly(D,L-lactide-co-glycolide) microspheres to sustain release. FDA first approved Byetta on 28 April 2005 and the EU authorised it on 20 November 2006. In the US, AstraZeneca notified FDA on 16 August 2024 of plans to discontinue Byetta and Bydureon BCise (Bydureon itself left the market in March 2021); FDA approved Amneal's generic exenatide injection (ANDA 206697) on 19 November 2024. Placebo-controlled 16- to 30-week trials showed HbA1c reductions when added to oral agents; EXSCEL (14,752 patients) found the once-weekly form non-inferior to placebo for major cardiovascular events but not superior (HR 0.91, 95% CI 0.83 to 1.00). It has no approved use outside type 2 diabetes; a phase 3 trial in Parkinson's disease reported no benefit and its paper now carries a journal Expression of Concern.

Evidence: Approved on the basis of phase 3 programmes in type 2 diabetes: placebo-controlled trials of the twice-daily form added to oral drugs (label section 14), DURATION-1 (once-weekly form gave a larger HbA1c fall than twice-daily, -1.9% vs -1.5%), and DURATION-6 (once-weekly exenatide failed non-inferiority against once-daily liraglutide, HbA1c -1.28% vs -1.48%). EXSCEL, a large cardiovascular outcomes trial, found no significant difference in major cardiovascular events (HR 0.91, 95% CI 0.83 to 1.00). Use in Parkinson's disease is unapproved: the UK phase 3 Exenatide-PD3 trial (194 people) found no benefit on motor scores at 96 weeks, and in June 2026 The Lancet published an Expression of Concern about that paper.[src][src][src][src][src][src]

Known safety signals

Bydureon BCise carries a boxed warning: exenatide extended-release causes thyroid C-cell tumours at clinically relevant exposures in rats, and it is unknown whether it does so in humans.[src]
Most common adverse reactions with Byetta added to metformin and/or a sulfonylurea were gastrointestinal: nausea in 44% versus 18% on placebo, vomiting 13% versus 4%, diarrhoea 13% versus 6%. Nausea usually decreases over time.[src]
With the extended-release form, the most common adverse reactions (5% or more) were injection-site nodules (10.5%) and nausea (8.2%).[src]
Acute pancreatitis, including fatal and non-fatal haemorrhagic or necrotising cases, has been observed with GLP-1 receptor agonists including Byetta; the label says to stop Byetta if pancreatitis is suspected.[src]
Hypoglycaemia risk rises when exenatide is combined with a sulfonylurea or insulin; the label notes the dose of those medicines may need to be reduced.[src]
Postmarketing reports include acute kidney injury (mostly after dehydration from vomiting or diarrhoea), drug-induced immune-mediated thrombocytopenia with serious and possibly fatal bleeding, serious hypersensitivity reactions and pulmonary aspiration during general anaesthesia or deep sedation.[src]

Around the world

Is Exenatide legal where you live?

Country	Status	What it means	Verified
Australia	Not approved	TGA assessed Byetta and Bydureon (2013), but a search of the ARTG on 29 Sep 2026 finds no current exenatide entry.Details →source	2026-09-29
Brazil	Not approved	No active registration: the Byetta and Bydureon registrations show as inactive in Anvisa's registerDetails →source	2026-09-29
Canada	Not approved	No exenatide product is authorised on the market; Byetta and Bydureon were cancelled in 2022Details →source	2026-09-29
China	Generics available	Approved, with a domestic generic approved in 2025; insurance covers it for type 2 diabetes.Details →source	2026-09-29
European Union	Approved	Authorised EU-wide for type 2 diabetes as Byetta (2006) and Bydureon (2011)Details →source	2026-09-29
India	Approved	Exenatide has an older CDSCO approval; whether it is still sold in India could not be confirmedDetails →source	2026-09-29
Japan	Unverified	Byetta (2010) and Bydureon (2012) were approved, but exenatide is off the current price list and its marketing status was not confirmedsource	2026-09-29
Mexico	Unverified	Bydureon's registration was cancelled in 2025; the status of Byetta could not be confirmedsource	2026-09-29
New Zealand	Not approved	Byetta and Bydureon approvals have lapsed; no exenatide product is currently approved or fundedDetails →source	2026-09-29
United Arab Emirates	Unverified	Could not confirm whether exenatide (Byetta, Bydureon) is registered by the EDE; no UAE-specific record was foundsource	2026-09-29
United Kingdom	Unverified	EU authorisations exist for Byetta and Bydureon; we could not confirm a current UK licence or availabilitysource	2026-09-29
United States	Generics available	Byetta and Bydureon BCISE are listed as discontinued; an FDA-approved generic exenatide (Amneal) is on the marketDetails →source	2026-09-29