Lancet

Exenatide shows no benefit in Parkinson's disease treatment

February 12, 2025

Study details: The phase 3, randomized Exenatide-PD3 trial (NCT04232969) included 194 participants with mild to moderate Parkinson's disease across six UK research hospitals. Participants were randomly assigned to receive either weekly exenatide injections or placebo for 96 weeks. Primary outcome was the change in the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score, off dopaminergic medication at 96 weeks.

Results: At 96 weeks, the MDS-UPDRS III off-medication scores worsened by a mean of 5.7 points in the exenatide group and 4.5 points in the placebo group (adjusted coefficient, 0.92 (95% confidence interval, -1.56 to 3.39; p=0.47). Serious adverse events occurred in 9% of the exenatide group and 11% of the placebo group, indicating no significant safety concerns.

Clinical impact: These findings suggest that exenatide should not be recommended as a disease-modifying treatment for Parkinson's disease. The results highlight the importance of large-scale trials in validating the efficacy of potential treatments and may redirect research efforts towards other therapeutic avenues. Authors call for studies with agents that show better target engagement or in specific patient subgroups to establish whether GLP-1 receptor agonists have any benefit in Parkinson's disease.

Source:

Vijiaratnam N, et al. (2025, February 4). Lancet. Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial. https://pubmed.ncbi.nlm.nih.gov/39919773/