Efficacy of GLP-1 receptor agonists in Parkinson’s disease: a systematic review and exploratory network meta-analysis of randomized controlled trials

Journal article : Review

Background: Current therapies for Parkinson’s disease lack proven disease-modifying effects. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), developed for type 2 diabetes, have shown potential neuroprotective properties. Their comparative efficacy in Parkinson’s disease remains unclear. Methods: A systematic search (inception–February 2026) identified randomized controlled trials evaluating GLP-1RAs in Parkinson’s disease. Pairwise and frequentist random-effects network meta-analyses were performed. The primary outcome was MDS-UPDRS Part III (ON state). Results: Five trials (n = 708) were included. Pairwise meta-analysis showed no significant overall improvement in MDS-UPDRS Part III (MD –2.00; 95% CI –5.46 to 1.46; I² = 80.5%). Network meta-analysis demonstrated significant ON-state motor improvement with Exenatide 20 µg/day (MD –9.80; 95% CI –14.47 to –5.13) and Lixisenatide 20 µg/day (MD –3.08; 95% CI –5.31 to –0.85). No significant effects were observed for MDS-UPDRS Part III (OFF-state) or other domains (Parts I, II, and IV; ON-state). NLY01 at 5 mg/week improved PDQ-39, while NMSS showed dose-dependent divergence. Gastrointestinal adverse events were more frequent with GLP-1RAs. Conclusion: GLP-1 receptor agonists may provide dose-specific motor benefits in Parkinson’s disease, but evidence for broader clinical improvement is limited. Larger, longer-duration trials are needed.

Authors: Ali, M; Sharma, A; Paruchuri, A; Shahzad, F; Khalid, MB

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer
• Journal: Neurological Sciences
• Volume: 47
• Issue: 5
• Pages: 432
• Article number: 432
• Publication date: 2026-04-17
• Acceptance date: 2026-02-21
• DOI: 10.1007/s10072-026-08929-1
• EISSN: 1590-3478
• ISSN: 1590-1874
• Language: English
• Keywords: GLP-1 receptor agonist (GLP-1RA); Quality of life; Parkinson’s disease; Cognition
• Subtype: Review