In Brief | Neurology | Parkinsons
Exenatide Once a Week Shows Promise as a Disease-Modifying Treatment for Parkinson's Disease
Time to read: 02: 23
Time to listen: 04:47
Originally Published: 22 February 2024
Sourced: Lancet
Type of article: In Brief
MedED Catalogue Reference: MIBRR002
Category: Neurology
Cross Reference: Parkinson's Diseases
Keywords: Parkinson's, exenatide, morbitiy and mortality
This Phase 3 trial suggests that exenatide once a week may offer potential as a disease-modifying treatment for Parkinson's disease, improving motor function compared to placebo.
This is a review of original research published in Lancet, 22 February 2025. This article does not represent the original research, nor is it intended to replace the original research. Unless otherwise references, all information contained in this review is referenced to the original work. Access the full Disclaimer Information.
In Context
Glucagon-like peptide-1 (GLP-1) receptor agonists have demonstrated neurotrophic effects in preclinical models of Parkinson's disease (PD). Epidemiological studies and small clinical trials have suggested that these agents, particularly exenatide, may slow PD progression. This study aimed to assess whether exenatide could modify disease progression in a larger, longer-term, multicentre trial.
The primary objective was to determine whether extended-release exenatide could slow the rate of motor progression in patients with PD over a 96-week period. The study also aimed to evaluate safety, tolerability, and any potential advantages in specific subgroups.
Study Methodology
They were randomly assigned (1:1) to receive weekly subcutaneous injections of either extended-release exenatide 2 mg or a placebo for 96 weeks.
Secondary outcomes were changes in MDS-UPDRS parts I–IV in the ON-medication state, the timed sit–stand–walk test in the OFF-medication and ON-medication states, the NMSS, PDQ-39, PHQ-9, EQ-5D-5L, MoCA, UDysRS, LEDD, and 3-day Hauser diary, as well as adverse events.
Statistical analyses followed an intention-to-treat approach using a linear mixed modelling method.
Findings
Between January 2020 and April 2022, 215 participants were screened, and 194 were enrolled (97 in each group).
The cohort included 56 (29%) females and 138 (71%) males.
A total of 92 participants in the exenatide group and 96 in the placebo group had at least one follow-up visit and were included in the final analysis.
The following findings were recorded:
The adjusted coefficient for exenatide’s effect was 0.92 (95% CI –1.56 to 3.39; p=0.47), indicating no significant difference between groups.
Nine (9%) participants in the exenatide group and 11 (11%) in the placebo group experienced at least one serious adverse event.
Discussion
While preclinical and smaller clinical studies suggested potential neuroprotective effects of GLP-1 receptor agonists, this trial found no evidence supporting exenatide as a disease-modifying treatment in PD.
The results contrast with prior findings from shorter-duration studies, which showed modest motor benefits. Importantly, this was the longest trial of any GLP-1 receptor agonist in PD and included the largest patient cohort to date. The findings suggest that longer exposure or higher target engagement may be necessary to detect benefits.
Further analyses will explore whether specific subgroups, defined by baseline biochemical markers, may respond better to treatment.
Conclusion
Exenatide was well tolerated but did not significantly alter motor progression in PD. Future studies should focus on alternative GLP-1 receptor agonists with improved brain penetration or higher receptor engagement, as well as further subgroup analyses to determine whether specific populations could benefit from such interventions.
Disclaimer
This article is compiled from several resources researched and compiled by the contributor. It is in no way presented as an original work. Every effort has been made to attribute quotes and content correctly. Where possible all information has been independently verified. The Medical Education Network bears no responsibility for any inaccuracies which may occur from the use of third-party sources. If you have any queries regarding this article contact us
Fact-checking Policy
The Medical Education Network makes every effort to review and fact-check the articles used as source material in our summaries and original material. We have strict guidelines in relation to the publications we use as our source data, favouring peer-reviewed research wherever possible. Every effort is made to ensure that the information contained here is an accurate reflection of the original material. Should you find inaccuracies, out of date content or have any additional issues with our articles, please make use of the contact us form to notify us.
