Weekly exenatide fails to slow Parkinson's in phase 3 trial; Lancet later flags paper
Exenatide, a GLP-1 drug distinct from semaglutide and tirzepatide, did not slow Parkinson's in a 194-person trial, and The Lancet has since flagged the published paper with an Expression of Concern.
People with Parkinson's disease who received once-weekly extended-release exenatide for 96 weeks worsened on a standard motor test by roughly the same amount as those given placebo, according to a phase 3 trial published in The Lancet on Feb. 4, 2025 [1]. The journal later attached an Expression of Concern to that paper, issued June 22, 2026 [2].
The study ran at six research hospitals in the United Kingdom. Screening took place between Jan. 23, 2020, and April 23, 2022; of 215 people screened, 194 were randomly assigned in equal groups to 2 mg of extended-release exenatide by subcutaneous pen injection once a week or a visually identical placebo [1]. Participants were 25 to 80 years old, had a Parkinson's diagnosis, were at Hoehn and Yahr stage 2.5 or lower while taking dopaminergic medication, and had been on that medication for at least four weeks before enrolling [1]. Fifty-six of the 194 (29%) were female and 138 (71%) were male [1].
The primary measure was the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale part III score, assessed off dopaminergic medication at 96 weeks. Scores rose, meaning motor symptoms got worse, by a mean of 5.7 points (SD 11.2) in the exenatide group and 4.5 points (SD 11.4) in the placebo group, giving an adjusted coefficient of 0.92 (95% CI -1.56 to 3.39; p=0.47) [1]. Ninety-two people in the exenatide group and 96 in the placebo group had at least one follow-up visit and were included in the analyses [1].
At least one serious adverse event was recorded for nine exenatide recipients (9%) and 11 placebo recipients (11%) [1]. The authors concluded that exenatide appeared safe and well tolerated, that they found no evidence supporting it as a disease-modifying treatment for Parkinson's, and that research using agents with better target engagement, or focused on specific patient subgroups, would be needed to show whether GLP-1 receptor agonists have any role in the disease [1].
The Michael J. Fox Foundation, which has funded GLP-1 research in Parkinson's, described the study as the largest and longest of a GLP-1 receptor agonist in the disease and said the findings "effectively close the door on the idea of exenatide as a treatment for Parkinson's" [4]. The foundation pointed out that a phase 2 trial of lixisenatide, another GLP-1 drug, reported in the New England Journal of Medicine in April 2024 that people taking it held largely steady while the placebo group continued to worsen, a small difference, and said more work is needed to understand why GLP-1 trials have produced differing results [4].
The Expression of Concern is indexed as a Lancet notice published June 27, 2026, in volume 407, issue 10548, page 2588, with electronic publication on June 22, 2026 [2]. The notice carries no abstract and gives no reason for the editors' concern, and it is labeled an Expression of Concern rather than a retraction [2].
Why it matters for patients
The result concerns exenatide in Parkinson's disease. Exenatide is a GLP-1 receptor agonist but a different molecule from semaglutide (Ozempic, Wegovy, Rybelsus) and tirzepatide (Mounjaro, Zepbound), and the trial tested exenatide alone [1][4]. GLP-1 drugs were developed to treat type 2 diabetes and to aid weight loss [4]. Parkinson's is not an approved use of exenatide or of other GLP-1 medicines on the strength of these results [4].
Whether other GLP-1 medications, which may behave differently in the body, could help in Parkinson's, or whether some groups of patients might respond while others do not, has not been established; the Michael J. Fox Foundation says both questions need more research [4].
Anyone who read coverage of the 2025 trial should also know the paper's status has changed. An Expression of Concern signals that editors are drawing attention to a published article, but this notice does not explain what prompted it, so the journal's specific concern has not been disclosed [2].
What happens next
The trial authors called for additional studies of other agents or of particular patient subgroups before conclusions are drawn about the GLP-1 class in Parkinson's disease [1]. The Michael J. Fox Foundation said results from further GLP-1 studies in Parkinson's were expected during 2025 [4]. Whether The Lancet will take any further action on the 2025 paper, and what its editors found, has not been reported [2].
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