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

Recent trends suggest exploring the repurposing of different drugs for Parkinson's disease patients (PD). One of these drugs is Glucagon-like peptide-1 (GLP-1), a medication used to treat type 2 diabetes mellitus. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of different forms of GLP-1 agonists on motor and non-motor functions of PD patients during ON-medication and OFF-medication states. A literature search was conducted through PubMed, Scopus, Web of Science, OVID, Cochrane Central, and Google Scholar using relevant keywords. Quality assessment was performed using the Risk of Bias-2 (RoB-2) domains. Statistical analysis included calculating the mean difference (MD) and the corresponding 95% confidence intervals (CIs) using Review Manager 5.4.1. Four randomized controlled trials (RCTs) testing three different forms of GLP-1 agonists with a total of 514 patients were included in the study. GLP-1 agonists significantly improved motor function during the OFF-medication state (MD =  - 3.29, 95% CI [- 5.17 to - 1.42], P = 0.0006). It does not show improvement in quality of life assessed by PDQ-39 (MD =  - 0.54, 95% CI [- 2.07 to 0.99], P = 0.49). None of the adverse effects stated in the RCTs were higher in the GLP-1 agonists group except for nausea (RR = 1.98, P = 0.0008), vomiting (RR = 6.65, P = 0.0008), constipation (RR = 1.45, P = 0.01), and weight loss (RR = 2.11, P = 0.03). This systematic review and meta-analysis provide evidence that GLP-1 agonists could improve the motor function of PD patients. However, safety is still of concern. Further high-quality studies with standardized protocols and larger sample sizes are needed to confirm our findings.