GLP‐1 receptor agonists for Parkinson's disease: An updated meta-analysis

Introduction

Treatments for Parkinson's disease (PD) focus on symptom reduction through dopaminergic therapies, without clear evidence of disease-modifying effects. Glucagon-like peptide-1 (GLP-1) receptor agonists may reduce neuroinflammation by decreasing microglia activation in PD. Clinical trials suggest these agents have disease-modifying potential in PD.

Objective

Evaluate the efficacy of GLP-1 receptor agonists in PD.

Methods

PubMed, Embase and Cochrane Library were searched to identify randomized controlled trials (RCTs) of GLP-1 agonists for PD, up to July 2024. The risk of bias was assessed using the RoB-2 tool, and statistical analysis was performed with RevMan 5.4.1 software.

Results

GLP-1 receptor agonists showed a beneficial effect on MDS-UPDRS part III motor scores compared to placebo. Off-medication state, there was a −1.22 point improvement (95%CI -2.46, 0.22; P = 0.05). On-medication state, scores improved by −2.52 points (95%CI -4.02, −1.01; P = 0.001). The global MDS-UPDRS score showed a −3.43-point difference (95%CI -6.48, −0.48; P = 0.02). Cognitive performance, assessed via the Mattis DRS-2, improved by 1.32 points (95%CI 0.16, 2.52; P = 0.03). There were no significant differences in the NMSS (−0,19; 95%IC -3,44, 3,05; P = 0.91), in MADRS (−1,04; 95%IC -2,57, 0,48; P = 0.18), or PDQ-39 (−0,91; 95%IC -2,22, 0,39; P = 0.17).

Conclusion

GLP-1 receptor agonists improved motor and cognitive performance in PD, suggesting potential symptomatic benefits. However, further studies are needed to evaluate their long-term effects and their role in disease modification, especially considering ethnic and disease severity variations.