To evaluate the efficacy and safety of Glucagon-like peptide-1 (GLP-1) receptor agonists for Parkinson's disease (PD).

PubMed, Scopus, and Cochrane Central were searched till September 2024. Risk ratios (RR) and Mean Difference (MD) with a 95% Confidence Interval (CI) were pooled for dichotomous and continuous outcomes using the Review Manager version 5.4.1. employing the random effects model. The quality of the included studies was assessed using the Cochrane RoB 2.0 tool.

Four randomized trials pooling 425 patients were included in this analysis. Compared to the placebo, GLP-1 receptor agonists significantly decreased MDS-UPDRS III score (off medication) (WMD= -3.29; 95%CI: [-5.14, -1.43]; p=0.0005; I²=0%) and increased the GI adverse event profile (RR: 1.85 [1.14, 3.01]; p=0.01; I²=0%). Other outcomes like the MDS-UPDRS I score (WMD= -0.34; 95%CI:[-1.53,0.85]; p=0.58; I²=52%), MDS-UPDRS II score (WMD= -0.18 ; 95%CI:[-1.04,0.68]; p=0.68; I²=20%), MDS-UPDRS III score (on medication) (WMD= -2.78; 95%CI:[-5.99,0.42]; p=0.09; I²=81%), MDS-UPDRS IV score (WMD= -0.06; 95%CI:[-0.41,0.28]; p=0.72; I²=0%), HRQoL (WMD= -0.58; 95%CI:[-2.32,1.16]; p=0.51; I²=0%); Mattis DRS score (WMD= 3.66; 95%CI:[-1.02,8.35]; p=0.12; I²=82%), MADRS score (WMD=-1.03 ; 95%CI:[-2.54,0.47]; p=0.18; I²=0%), serious adverse events (RR=1.50, 95%CI:[0.56,4.04]; p=0.42; I²= 9%) and weight loss (WMD= 2.17 ; 95%CI:[0.60,7.76]; p=0.24; I²=58%) were comparable between the two groups.

According to our analysis, GLP-1 receptor agonists are a potentially effective therapy for Parkinson's disease, with improvements seen in MDS-UPDRS III score but with a worse GI safety profile. More trials are needed to reach a definitive conclusion.