GLP-1 receptor agonists fail to improve Parkinson's motor function, increase GI adverse events.

While Parkinson's disease (PD) lacks proven disease-modifying therapies, shared pathways with Type 2 diabetes, including insulin resistance and neuroinflammation, have made glucagon-like peptide-1 receptor agonists (GLP-1 RAs) a promising area of research. Preclinical models showed neuroprotective potential for GLP-1 RAs, which activate the GLP-1R pathway. However, clinical trial results have been conflicting, necessitating a systematic evaluation to distinguish between symptomatic relief and true disease modification in the broader PD population.

This meta-analysis systematically evaluated four high-quality randomized, double-blind, placebo-controlled trials of GLP-1 RAs in idiopathic PD, comprising 667 patients. Researchers searched PubMed, Scopus, Web of Science, Cochrane Library, and Embase through November 2025. The primary endpoint was motor function, assessed by the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (motor examination). Analysis used a random-effects model, strictly stratified by "ON" versus "OFF" medication states, to assess efficacy and safety.

GLP-1 RAs demonstrated no significant improvement in motor function. In the OFF-medication state, the mean difference (MD) was -0.69 (95% CI -2.81 to 1.43; p=0.52), and in the ON-medication state, the MD was -0.86 (95% CI -3.35 to 1.63; p=0.50).

No meaningful benefits were observed for non-motor symptoms, cognition, or quality of life across the 667 patients included in the analysis. Conversely, treatment with GLP-1 RAs significantly increased gastrointestinal adverse events. The risk ratio (RR) for nausea was 2.48, for vomiting 4.53, and for clinically concerning weight loss 3.32. These findings suggest a clear lack of benefit for the primary motor outcome and other key secondary outcomes, alongside a notable increase in adverse effects.