Exenatide fails to slow Parkinson's disease in a phase 3 trial

A large UK trial found that the GLP-1 receptor agonist exenatide did not slow the progression of Parkinson's disease. The results, published in The Lancet on Feb 4, 2025, showed no meaningful difference between weekly exenatide injections and placebo on the trial's main measure of motor symptoms after 96 weeks ^[1][4]. More than a year later, on June 22, 2026, The Lancet's editors published an Expression of Concern about the paper ^[2].

What the trial tested

Exenatide-PD3 was a phase 3, multicenter, double-blind, placebo-controlled trial run at six research hospitals in the UK ^[1]. Researchers screened 215 people and randomly assigned 194 of them, in equal numbers, to receive either extended-release exenatide 2 mg by subcutaneous pen injection once a week for 96 weeks or a visually identical placebo ^[1]. Participants were aged 25 to 80, had Parkinson's disease at Hoehn and Yahr stage 2.5 or less while on dopamine medication, and had been on dopaminergic treatment for at least four weeks before enrolling ^[1]. Of the participants, 56 (29%) were female and 138 (71%) were male ^[1]. Enrollment ran from Jan 23, 2020 to April 23, 2022 ^[1], and the study concluded in the summer of 2024 ^[4].

The main outcome was the MDS-UPDRS part III score — a rating of motor symptoms — measured off dopamine medication at 96 weeks ^[1]. Higher scores mean worse motor function.

The numbers

At 96 weeks, MDS-UPDRS III off-medication scores had worsened by an average of 5.7 points (SD 11.2) in the exenatide group and 4.5 points (SD 11.4) in the placebo group ^[1]. The adjusted coefficient for the effect of exenatide was 0.92 (95% CI −1.56 to 3.39; p=0.47) — a result consistent with no benefit ^[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 analysis ^[1].

On safety, 9 participants (9%) in the exenatide group had at least one serious adverse event, compared with 11 (11%) on placebo ^[1]. The authors concluded that exenatide appeared safe and well tolerated but that they found no evidence supporting it as a disease-modifying treatment for Parkinson's ^[1]. They wrote that studies using agents with better target engagement, or in specific subgroups, are needed to determine whether GLP-1 receptor agonists have any role in Parkinson's ^[1]. The trial was funded by the UK's National Institute for Health and Care Research and the charity Cure Parkinson's ^[1].

The Michael J. Fox Foundation described the study as the largest and longest test to date of a GLP-1 receptor agonist in people with Parkinson's, and said the results "effectively close the door" on exenatide specifically as a Parkinson's treatment, while leaving open questions about other GLP-1 drugs ^[4]. The foundation noted that an earlier phase 2 trial of a different GLP-1 drug, lixisenatide, published in the New England Journal of Medicine in April 2024, had found that people on the drug held largely steady on their test score while the placebo group progressed — a small difference, and one that conflicts with the exenatide result ^[4].

The Expression of Concern

On June 22, 2026, The Lancet's editors published an Expression of Concern about the Exenatide-PD3 paper, appearing in the June 27, 2026 print issue ^[2]. An Expression of Concern is a notice journals use to alert readers to questions about a published article. The sources provided here do not include the text of the notice, so the specific reason for it is not yet known from these documents ^[2].

Why it matters for patients

Exenatide is a GLP-1 receptor agonist, the same drug class as semaglutide (Ozempic, Wegovy, Rybelsus). Interest in these drugs for brain diseases grew from laboratory work, epidemiology and small trials suggesting possible neurological benefits ^[1]. This trial is the field's first phase 3 test of a GLP-1 drug for a neurodegenerative disease ^[1], and it did not show a benefit for Parkinson's motor progression.

That is relevant to anyone who has heard that GLP-1 medicines might protect the brain. On the evidence in this trial, that claim is not supported for exenatide in Parkinson's. Results for one molecule do not automatically apply to others, and researchers say different formulations and more carefully selected patient groups still need testing ^[1][4]. The Expression of Concern adds uncertainty about how much weight to give this particular paper until the journal says more.

What happens next

The Michael J. Fox Foundation said results from some additional GLP-1 studies in Parkinson's were due in 2025, and that the foundation has funded more than a dozen GLP-1 projects since 2007 totaling roughly $5 million ^[4]. What action, if any, The Lancet will take after its June 2026 notice is not stated in the available sources ^[2].