Glucagon-like peptide-1 receptor agonists and the risk of Parkinson's disease in patients with type 2 diabetes: a systematic review and meta-analysis of large-scale real-world data
Abstract
Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder, yet effective disease-modifying therapies remain elusive. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used in the management of type 2 diabetes mellitus (T2DM), have shown neuroprotective potential in preclinical studies. However, real-world evidence on the association between GLP-1RAs use and PD risk remains inconsistent and has not been systematically synthesized. This systematic review and meta-analysis aimed to evaluate this association using large-scale real-world data.
Methods: We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science from database inception to March 18, 2026, for cohort and case-control studies exploring the association between GLP-1RA exposure and PD risk among patients with T2DM. Study selection, data extraction, and methodological quality assessment were independently conducted by two reviewers. All meta-analyses were performed using Stata 15.0 software.
Results: A total of six studies were included, involving 452,763 participants. The meta-analysis revealed that GLP-1RA exposure was significantly associated with a reduced risk of PD in patients with T2DM (HR = 0.68, 95%CI (0.54,0.85), P = 0.001). Subgroup analyses demonstrated that compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, and other hypoglycemic drugs, GLP-1RAs were linked to a lower risk of incident PD (DPP-4 inhibitors: HR = 0.60, 95%CI…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 452,763 participants or records.
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