Abstract
BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder with no currently approved disease-modifying treatments. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally used in type 2 diabetes, have demonstrated neuroprotective and anti-inflammatory effects in preclinical PD models. This systematic review and meta-analysis evaluated the efficacy and safety of GLP-1RAs in patients with PD. METHODS: A systematic search of MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov was conducted through July 2025 for randomized controlled trials (RCTs) comparing GLP-1RAs to placebo in PD. Primary outcomes included MDS-UPDRS Part III (motor examination) both on and off medication. Secondary outcomes included MDS-UPDRS Parts I, II, IV, PDQ-39, NMSS, and adverse effects. Data were pooled using a random-effects model with results reported as mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CI). RESULTS: Five RCTs involving 708 participants were included. No statistically significant differences were found in MDS-UPDRS Part III scores off medication (MD: -2.00, 95% CI: -4.12 to 0.11, p = 0.06) or on medication (MD: -1.40, 95% CI: -3.42 to 0.62, p = 0.17). Secondary outcomes also showed no significant benefits with GLP-1RA use. However, GLP-1RAs were associated with increased gastrointestinal side effects, including nausea (RR: 2.09), vomiting (RR: 4.53), constipation (RR: 1.60), and weight loss (RR: 1.83). CONCLUSION: Current evidence does not demonstrate a statistically significant overall benefit of GLP-1RAs on efficacy outcomes in PD, while gastrointestinal adverse events are increased. More trials are needed to clarify their disease-modifying potential.