GLP-1 does not slow Parkinson’s disease progression in phase 3 study
Key takeaways:
- Previous studies suggest GLP-1 receptor agonists may benefit those with Parkinson’s disease.
- A phase 3 randomized controlled trial found no significant improvements with the GLP-1 exenatide in this population.
Treatment with exenatide, a GLP-1 receptor agonist, was comparable to placebo in slowing the rate of Parkinson’s disease progression over 96 weeks of treatment, according to a phase 3 study published in The Lancet.
“Exenatide is a licensed and effective treatment for type 2 diabetes. It is a GLP-1 receptor agonist and stimulates insulin release in the presence of elevated blood glucose,” Nirosen Vijiaratnam, MD, from the department of clinical and movement neurosciences, Queen Square Institute of Neurology, University College London, and colleagues wrote.
GLP-1 receptor agonists may possess certain neurotrophic properties that delay disease progression, Vijiaratnam and colleagues wrote. Small, randomized trials have suggested that these agents may lower the risk for and slow progression of PD. So, Vijiaratnam and colleagues conducted a phase 3 clinical trial to further examine the efficacy of exenatide in patients with PD.
Their multicenter, double-blind, parallel-group, randomized, placebo-controlled study was conducted at six research hospitals in the United Kingdom, and included 194 adults diagnosed with PD (mean age, 60.7 years; 71% men). All participants were at Hoehn and Yahr stage 2.5 or less when on dopaminergic medication or taking dopamines for at least 4 weeks prior to enrollment.
The participants were randomly assigned on a 1:1 basis to either receive self-administered 2 mg extended-release subcutaneous injection of exenatide or placebo once a week for 96 weeks.
The primary outcome was score on the Movement Disorder Society revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III when off dopaminergic medication at 96 weeks. Secondary outcomes included changes in MDS-UPDRS when on dopamine-based medication, as well as off-and-on state analysis of timed sit-stand-walk tests and scores from a battery of neuropsychological exams.
The researchers reported that 188 enrollees — 92 in the exenatide group and 96 in the placebo group — recorded at least one follow-up visit and were subsequently included in primary outcome analysis.
At 96 weeks, Vijiaratnam and colleagues reported that MDS-UPDRS III “off”-medication scores increased by a mean of 5.7 points in the exenatide group and 4.5 points in the placebo group.
They noted, however, that no significant differences with respect to the primary study outcome were found between groups in the modified intention-to-treat population.
Regarding secondary outcomes, the researchers reported no significant differences between groups in MDS-UPDRS scores during “on” time, or on the neuropsychological battery.
Data further revealed exenatide was generally safe and well-tolerated. Nine participants in the treatment group recorded at least one serious adverse event compared with 11 given placebo.
“It is not yet clear whether there may be a subgroup of people with Parkinson’s disease who may get benefit from the use of exenatide,” Thomas Foltynie, BSc, MBBS, PhD, professor of neurology in the department of clinical and movement neurosciences at the University College London Institute of Neurology, said in a release related to the study. “We will continue to scrutinize the data to see whether abnormal blood test results such as having ‘pre-diabetes’ might predict a better response to exenatide and whether there were more of these people in the earlier, smaller trials in which we found positive overall effects.”
Reference:
GLP-1 drug shows little benefit for people with Parkinson’s disease. https://www.ucl.ac.uk/news/2025/feb/glp-1-drug-shows-little-benefit-people-parkinsons-disease. Published Feb. 3, 2025. Accessed Feb. 4, 2025.