GLP-1 receptor agonists in Parkinson's disease progression: a meta-analysis with trial sequential analysis of randomized controlled trials.

BACKGROUND

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as potential neuroprotective agents for Parkinson's disease (PD). However, evidence regarding their efficacy remains inconclusive.

OBJECTIVE

To assess the therapeutic effects and safety profile of GLP-1 RAs in patients with mild-to-moderate PD. We aim to conduct an updated systematic review to evaluate the effects of GLP-1 RAs in patients with mild-to-moderate PD.

DESIGN

Systematic review and meta-analysis of randomized controlled trials (RCTs) with trial sequential analysis (TSA) and Grading of Recommendations, Assessment, Development, and Evaluations certainty assessment.

DATA SOURCES: PubMed, Embase, and the Cochrane Library were searched through April 14, 2025.

METHODS

We conducted a systematic review and meta-analysis of RCTs with TSA comparing GLP-1 RAs to placebo in patients with mild-to-moderate PD. The primary outcome was change in the Movement Disorder Society-unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores.

RESULTS

Five RCTs involving a total of 708 nondiabetic patients with mild-to-moderate PD were included. GLP-1 RAs significantly attenuated motor symptom progression, as evidenced by a mean difference in MDS-UPDRS Part III (off medication) of -2.06 (95% confidence interval (CI): -4.09; -0.03; I 2 = 56%), with conclusive evidence supported by TSA. No statistically significant improvements were observed in other MDS-UPDRS domains, levodopa equivalent daily dose reduction, or functional scales (Parkinson's Disease Questionnaire-39, Non-Motor Symptoms Scale for Parkinson's Disease, UDysRS). A nonsignificant trend toward increased serious adverse events or treatment discontinuation was observed (odds ratio = 1.52; 95% CI: 0.66; 3.50), with low heterogeneity. TSA for secondary outcomes indicated that additional trials are required.

CONCLUSION

GLP-1 RAs may provide a modest benefit in slowing motor progression in PD. However, their effects on nonmotor symptoms, medication use, and long-term safety remain uncertain due to the limited number of available trials. Further large-scale, long-duration trials are warranted.

TRIAL REGISTRATION: INPLASY2024110119.