Objective: To assess the safety and effectiveness of GLP-1 RAs in patients with PD.

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. While current therapies address symptom management, there is an unmet need for disease-modifying treatments. Glucagon-like peptide-1 receptor agonists(GLP-1 RAs), initially developed for diabetes, have shown neuroprotective properties, including the inhibition of cytokine-mediated apoptosis and stimulation of neurogenesis.

Method: We followed PRISMA guidelines. We included all randomized controlled trials (RCTs) evaluating GLP-1 receptor agonists in PD that were identified through comprehensive searches of PubMed, SCOPUS, Web of Science, and Cochrane Library. Cochrane’s risk-of-bias tool was used to assess the RCTs’ quality. A random-effects model was used, calculating mean differences (MDs) and risk ratios (RRs) with their confidence intervals (CIs).

Results: Five RCTs met the inclusion criteria. The meta-analysis revealed that GLP-1 RAs led to a statistically significant, albeit modest, overall improvement in motor symptoms (MDS-UPDRS Part III) compared to control, both in the ON-medication state (MD -1.33; P=0.01) and the OFF-medication state (MD -2.22; P=0.01). However, these overall findings, marked by substantial heterogeneity, were not consistently supported at individual follow-up durations; specifically, for the ON-medication state, no single time point demonstrated a statistically significant motor benefit. For the OFF-medication state, only the 60-week follow-up showed a significant improvement (MD -3.29; P=0.0005), with other time points not reaching significance. No statistically significant differences were found for health-related quality of life (PDQ-39), other MDS-UPDRS domains (Part I, II, IV), or Levodopa equivalent daily dose. GLP-1 RAs were associated with significantly higher rates of gastrointestinal adverse events and weight loss.

Conclusion: GLP-1 RAs showed some benefits in UPDRS-III, but didn’t reach the minimally clinically important difference. The safety profile necessitates careful monitoring. Further trials are required to confirm these results and define their therapeutic role.

« Back to 2025 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/therapeutic-potential-of-glp-1-receptor-agonists-in-parkinsons-disease-a-systematic-review-and-meta-analysis/