First approved GLP-1 agonist, based on a peptide from Gila monster saliva. It was used in type 2 diabetes; it has now been withdrawn in the US and the EU for commercial reasons and has been studied in Parkinson's disease.
FDA (US): Approved (2005, Byetta, twice daily; 2012, Bydureon weekly; 2017, Bydureon BCise) for type 2 diabetes. Withdrawn from the US market by the manufacturer in October 2024 (Byetta and Bydureon BCise)
EMA (EU): Approved (2006, Byetta; 2011, Bydureon) for type 2 diabetes. Authorizations withdrawn on January 1, 2026 at the request of the holder for commercial reasons
Dose
Type 2 diabetes: Byetta 5 µg subcutaneously twice a day before meals, increasing to 10 µg after a month; Bydureon 2 mg subcutaneously once a week (FDA/EMA label). In the Parkinson's trials, 2 mg weekly was used. It is no longer marketed in the US or the EU.
Safety
Nausea, vomiting, and diarrhea; nodules at the injection site with the weekly form. Risk of pancreatitis, kidney damage from dehydration, and gallbladder problems. The weekly form is contraindicated with a history of medullary thyroid cancer or MEN2. Do not use in severe renal impairment.
Interactions
It slows gastric emptying and may alter the absorption of oral drugs. May raise INR with warfarin. Greater risk of hypoglycemia with insulin or sulfonylureas.
Differences between women and men
The labels do not recommend its use in pregnancy; in the EU it was advised to stop Bydureon at least 3 months before trying to conceive because of its slow elimination. In the phase 3 Parkinson's trial, only 29% of participants were women. View the study →
Effect by goal · level of evidence
Cardiovascular safety in type 2 diabetes
no clear effectHighRCT (AA)in people
EXSCEL trial with about 14,700 people with type 2 diabetes and weekly exenatide. It showed that it does not increase cardiovascular events, but the observed reduction did not reach statistical significance.
Parkinson's disease: motor symptoms in a phase 2 trial
improvesLow-moderateRCT (AA)in people
−3.5 points MDS-UPDRS III
Trial with 62 patients and exenatide 2 mg weekly for 48 weeks. After 12 weeks without treatment, the motor scale (MDS-UPDRS III) was 3.5 points better than with placebo.
Parkinson's disease: no modifying effect in phase 3
no clear effectModerateRCT (AA)in people
No difference vs placebo
Exenatide-PD3 trial with 194 patients over 96 weeks. The motor scale worsened similarly with exenatide and with placebo (5.7 vs 4.5 points; no difference). In 2026 the journal published an expression of concern about this article.
It activates the GLP-1 receptor: it increases insulin when glucose is high, suppresses glucagon, slows gastric emptying, and reduces appetite. It partly crosses the blood-brain barrier, so it was investigated whether it protected neurons in Parkinson's disease.
What the evidence says
In people
Cardiovascular safety in type 2 diabetes. EXSCEL trial with about 14,700 people with type 2 diabetes and weekly exenatide. It showed that it does not increase cardiovascular events, but the observed reduction did not reach statistical significance. PubMed 28910237
Parkinson's disease: motor symptoms in a phase 2 trial. Trial with 62 patients and exenatide 2 mg weekly for 48 weeks. After 12 weeks without treatment, the motor scale (MDS-UPDRS III) was 3.5 points better than with placebo. PubMed 28781108
Parkinson's disease: no disease-modifying effect in phase 3. Exenatide-PD3 trial with 194 patients over 96 weeks. The motor scale worsened similarly with exenatide and with placebo (5.7 versus 4.5 points; no difference). In 2026 the journal published an expression of concern about this article. PubMed 39919773