Title: Do SGLT2 Inhibitors Influence Parkinson’s Disease Risk? A Meta-analysis of Randomized Trials (P6-17.012)
Authors: Theres Boby Alexander, Jamir Pitton Rissardo, Ana Leticia Fornari Caprara, and Ian M. Walker
Conference: 2026 AAN, Chicago, IL
Objective
To evaluate whether sodium-glucose cotransporter-2 (SGLT2) inhibitors influence the risk of Parkinson’s disease (PD) in patients with diabetes, heart failure, or chronic kidney disease.
Background
SGLT2 inhibitors have transformed the management of type 2 diabetes and heart failure by reducing cardiovascular events and slowing kidney disease progression. Preclinical studies suggest neuroprotective effects. Given shared metabolic and inflammatory pathways between diabetes and PD, SGLT2 inhibitors may influence PD risk.
Design/Methods
A systematic search of ClinicalTrials.gov identified randomized controlled trials reporting PD incidence in SGLT2 inhibitor versus placebo arms. No eligible data were found for ertugliflozin, enavogliflozin, henagliflozin, ipragliflozin, luseogliflozin, or tofogliflozin. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects Mantel-Haenszel model, and heterogeneity was assessed with the I² statistic.
Results
Fourteen trial arms from 12 unique studies (n ≈ 64,000; follow-up 7–50 months) were included. Two arms were excluded from pooled analysis due to zero events in both groups. The pooled OR for PD was 0.55 (95% CI: 0.27–1.12; p = 0.20). Heterogeneity was negligible (I² = 0%), and the prediction interval ranged from 0.23 to 1.50. Subgroup analyses showed no significant effect for individual agents: empagliflozin 10 mg (OR 0.64, 95% CI 0.17–2.43), empagliflozin 25 mg (OR 0.33, 95% CI 0.01–8.15), dapagliflozin 10 mg (OR 0.33, 95% CI 0.09–1.23), sotagliflozin (OR 0.25, 95% CI 0.03–2.24), canagliflozin 100 mg (OR 3.00, 95% CI 0.31–28.81), and bexagliflozin (OR 1.50, 95% CI 0.06–36.99). No evidence of publication bias was detected (Egger’s p = 0.96).
Conclusions
SGLT2 inhibitors do not significantly alter the risk of PD. These findings support their neurological safety, though longer follow-up and dedicated neurodegenerative outcome trials are warranted.
Citation
Alexander TB, Rissardo JP, Caprara AL, Walker IM. Do SGLT2 Inhibitors Influence Parkinson’s Disease Risk? A Meta-analysis of Randomized Trials (P6-17.012). Neurology 2026;106(11_suppl_1):862. doi: 10.1212/WNL.0000000000213157.
Figure 1. Forest plot of randomized trials evaluating SGLT2 inhibitors and Parkinson’s disease risk, showing no significant association (OR 0.55; 95% CI 0.27–1.12) with negligible heterogeneity.