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Background <p>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.</p> Methods <p>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).</p> Results <p>Five trials (<i>n</i> = 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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月17日

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  • Muaz Ali,
  • Arkansh Sharma,
  • Amith Paruchuri,
  • Faizan Shahzad,
  • Marwah Bintay Khalid,
  • Karthik N. B.,
  • Mona Avanaki,
  • Allimuthu Nithyanandam,
  • Tarannum Khan,
  • Vinay Suresh

摘要

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.