Comparative risk of epilepsy with SGLT2 inhibitors versus incretin-based therapies in type 2 diabetes

Objective: This study was undertaken to compare the risk of seizures and epilepsy among patients with type 2 diabetes (T2D) initiating sodium-glucose cotransporter-2 inhibitors (SGLT2is), glucagonlike peptide-1 receptor agonists (GLP-1 RAs), or dipeptidyl peptidase-4 (DPP-4) inhibitors using nationwide real-world data. Methods: Using propensity score matching, we identified 20 096 matched pairs of SGLT2i and DPP-4 inhibitor users, 8671 matched pairs of SGLT2i and GLP-1 RA users, and 1611 matched pairs of GLP-1 RA and DPP-4 inhibitor users from the Taiwanese National Health Insurance Research Database, spanning January 1, 2000 to December 31, 2021. Cox proportional hazards model was used to compare outcome risks between the respective treatment groups. Results: SGLT2i users had significantly lower cumulative incidences of seizure, epilepsy, and the composite outcome compared to DPP-4 inhibitor users (log-rank p <.001). Adjusted hazard ratios (aHRs) were.49 for seizure,.38 for epilepsy, and.46 for the composite outcome. Compared to GLP-1 RA users, SGLT2i users had a lower risk of the composite outcome (aHR =.66, p =.016), but not individual seizure or epilepsy outcomes. No significant differences were found between GLP-1 RAs and DPP-4 inhibitors. Significance: In this population-based study, SGLT2i use among patients with T2D was associated with lower risks of seizure and epilepsy compared to DPP-4 inhibitors, and lower composite seizure/epilepsy risk compared to GLP-1 RAs. These findings suggest a potential association between SGLT2i use and a lower risk of seizure- and epilepsy-related outcomes.