Efficacy and safety of GLP-1 receptor agonists in Parkinson's disease: a systematic review and meta-analysis of randomized clinical trials

Clinical Snapshot

Key Findings

• P Value: P = 0.01 for PDQ-39; non-significant for motor outcomes

• Effect Size: Mean difference: -0.75 points (PDQ-39 only significant outcome)

• Primary Outcome: No statistically significant difference in MDS-UPDRS Part III motor scores between GLP-1RAs and placebo

• Nnt Or Sensitivity: Clinical significance of 0.75-point PDQ-39 improvement questionable given minimal clinically important difference typically 4-7 points

• Confidence Interval: 95% CI: [-1.34, -0.17] for PDQ-39

Clinical Application

GLP-1RAs readily available but associated with significant gastrointestinal adverse events limiting tolerability GLP-1RAs available on PBS for diabetes; off-label use in Parkinson's disease not supported by current evidence and would require private prescription with significant cost implications Patients with Parkinson's disease considering adjunctive neuroprotective therapies

Abstract

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder with no proven disease-modifying therapies to date. Because changes in cerebral glucose metabolism and insulin resistance have been linked to PD pathophysiology, glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for diabetes, have been investigated as potential neuroprotective treatments. METHODS: This study systematically assessed the efficacy and safety of GLP-1RAs in PD through a systematic review and meta-analysis of randomized controlled trials identified in PubMed, Embase, and the Cochrane Library. The primary outcomes were motor function improvements measured by the MDS-UPDRS Part III in both on- and off-medication states at study endpoints and at intermediate timepoints of interest. Secondary outcomes included MDS-UPDRS Parts I, II, and IV, quality of life assessed by the PDQ-39, levodopa equivalent daily dose (LEDD), and the occurrence of adverse events. RESULTS: The meta-analysis found no statistically significant difference in favor of GLP-1RAs over placebo for motors and non-motors outcomes, except for PDQ-39 (MD: - 0.75; 95% CI: [- 1.34, - 0.17], P = 0.01). Regarding safety, GLP-1RAs were associated with a higher incidence of adverse events, especially gastrointestinal effects such as nausea, vomiting, and constipation. CONCLUSIONS: Overall, current evidence does not demonstrate consistent clinical benefit of using GLP-1RAs for treating motor or non-motor symptoms in PD nor support GLP-1RAs as disease-modifying therapy, underscoring the need for further research.

References

1. 1.Mendonça, M. F., Interaminense, A. C., do R Barros, G. S. T., Rabelo, L. A., de Oliveira, P. G., Sales, R. F., de C Lyra, A. M. V., & de S E Silva, H. R. (2024). Efficacy and safety of GLP-1 receptor agonists in Parkinson's disease: a systematic review and meta-analysis of randomized clinical trials. Neurological Sciences. https://doi.org/10.1111/cns.14341