The Lancet has issued an Expression of Concern (EOC) over a Phase 3 clinical trial evaluating once-weekly exenatide — a GLP-1 receptor agonist — as a potential disease-modifying treatment for Parkinson’s disease, according to the notice published at DOI 10.1016/S0140-6736(26)01241-9 (PMID: 42330995).
The trial in question — known as Exenatide-PD3 — was a multicenter, double-blind, randomized, placebo-controlled study conducted across six hospitals in the United Kingdom. Led by researchers at University College London and funded by the National Institute for Health and Care Research, the trial enrolled 194 participants with Parkinson’s disease who received either subcutaneous once-weekly exenatide or placebo over 96 weeks. The primary endpoint was change in the MDS-UPDRS Part III motor score, assessed in the off-dopaminergic-medication state at 96 weeks.
When results were published in The Lancet in February 2025 (DOI: 10.1016/S0140-6736(24)02808-3), the trial did not meet its primary endpoint: no statistically significant difference was found between the exenatide and placebo arms at 96 weeks. A secondary observation — a modest motor improvement in the exenatide group at the 60-week timepoint — drew attention but was not sufficient to support a disease-modifying conclusion.
The EOC signals that The Lancet’s editors have concerns about aspects of the paper and that an investigation is underway. The notice does not constitute a retraction. The specific nature of the editors’ concerns, the scope of the investigation, and its timeline are not disclosed in the EOC itself — which is standard practice at this stage of a journal inquiry.
The stakes are notable. Parkinson’s disease remains without any approved disease-modifying therapy. The hypothesis that GLP-1 receptor agonists might confer neuroprotection has drawn substantial scientific and commercial interest, and the Exenatide-PD3 study was the first Phase 3 test of that hypothesis in a neurodegenerative disease. An EOC does not change clinical guidance and should not alter patient or prescriber decisions; it is a signal that editors are reviewing evidence — not a finding of misconduct or error.
The investigation’s outcome is pending. The Vital Record will update this story as further information becomes available.