GLP-1 receptor agonists in Parkinson's disease: a meta-analysis revealing motor benefit and highlighting mood improvement.

BACKGROUND: GLP-1 receptor agonists (GLP-1RAs) show promise for Parkinson's disease (PD), but their comprehensive efficacy and safety profiles remain unclear. METHODS: We conducted a meta-analysis of 8 randomized trials ( = 850 PD patients) evaluating GLP-1RAs (Exenatide, Lixisenatide, Liraglutide, NLY01) versus placebo over treatment periods of 36-52 weeks and follow-up durations of 8-12 weeks (except one study with a 12-month follow-up). Outcomes included motor/non-motor symptoms assessed by validated scales and adverse events. RESULTS: GLP-1RAs significantly improved motor function post-treatment (SMD = -0.21, 95% CI -0.35 to -0.07,  = 0.003;  = 70.2%) and at follow-up (SMD = -0.32, 95% CI -0.55 to -0.08,  = 0.009;  = 48.5%). Exploratory analyses suggested an association between GLP-1RA treatment and improved mood outcomes post-treatment (SMD = -0.36, 95% CI -0.58 to -0.14,  = 0.001;  = 54.0%) and sustained at follow-up (SMD = -0.27, 95% CI -0.48 to -0.06,  = 0.013;  = 0.0%). Cognitive function improved during follow-up (SMD = -0.34, 95% CI -0.50 to -0.18,  < 0.001;  = 1.1%). Weight loss (OR = 3.87, 95% CI 1.88 to 7.94,  < 0.001;  = 47.7%) and gastrointestinal disorders (OR = 2.85, 95% CI 2.29 to 3.54,  < 0.001;  = 32.4%) were more frequent with GLP-1RAs, but PD symptom exacerbation was reduced (OR = 0.60, 95% CI 0.38 to 0.94,  = 0.025; = 0.0%). CONCLUSION: GLP-1RAs provide multidimensional benefits in PD, extending beyond motor control to mood and cognition. These findings support their therapeutic repurposing, with side effects being manageable. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251170531, CRD420251170531.