Title: Parkinson’s disease risk in patients using metformin versus other antidiabetic agents: A meta-analysis of observational studies
Authors: Jamir Pitton Rissardo, Ana Leticia Fornari Caprara
Conference: 7th WPC, Phoenyx, AZ
Objective
To evaluate whether metformin use is associated with altered risk of Parkinson’s disease compared to other antidiabetic treatments.
Background
Emerging evidence suggests that type 2 diabetes mellitus may influence neurodegenerative processes, including Parkinson’s disease (PD). Metformin, a widely used antidiabetic drug, has been hypothesized to exert neuroprotective effects. However, comparative risk estimates across different glucose-lowering agents remain unclear.
Design/Methods
A systematic review and meta-analysis was conducted using PubMed-indexed observational studies comparing PD incidence among patients treated with metformin versus alternative antidiabetic therapies. Six studies (2012–2025) were included, encompassing over 500,000 participants. Risk ratios (RR) were pooled using a random-effects model (DerSimonian-Laird) with Mantel-Haenszel weighting. Subgroup analyses were performed by comparator drug class. Heterogeneity was assessed using I² and Cochran’s Q. Publication bias was evaluated via Egger’s test and trim-and-fill method.
Results
The overall pooled random-effects estimate showed no significant association between metformin use and PD risk (RR = 0.30; 95% CI: 0.47 to 1.08; p = 0.44), with substantial heterogeneity (Q = 284.07, p < 0.001). Subgroup analyses revealed reduced PD risk for metformin versus insulin (RR = 0.32; 95% CI: 0.05 to 0.95) and versus no-metformin (RR = 0.11; 95% CI: 0.59 to 0.92), but increased risk compared to SGLT2 inhibitors (RR = 1.17; 95% CI: 1.02 to 1.31). Trim-and-fill analysis suggested potential publication bias, with three missing studies and an adjusted effect estimate shifting toward null.
Conclusions
Metformin may confer differential PD risk depending on comparator therapy, with possible protective effects versus insulin and no-metformin, but higher risk compared to SGLT2 inhibitors. High heterogeneity and evidence of publication bias warrant cautious interpretation. Further prospective studies are needed to clarify metformin’s neuroprotective potential.
Citation
Rissardo JP, Caprara ALF. Parkinson’s disease risk in patients using metformin versus other antidiabetic agents: A meta-analysis of observational studies. J Parkinsons Dis 2026;16(1_suppl):71-72. doi: 10.1177/1877718X261451755.
Figure 1. Forest plot with subgroup analyses, L’Abbé and Galbraith plots assessing heterogeneity, effect size distribution, and comparative risks across metformin versus alternative therapies.