Association between use of sodium-glucose cotransporter-2 inhibitors and epilepsy: A population-based study using target trial emulation

Objective: Preclinical studies in animals suggested potential neuroprotective effects of sodium-glucose co-transporter 2 inhibitors (SGLT-2i), but no epidemiological study has investigated the potential effects of SGLT-2i on epilepsy risk. We aimed to assess the association between use of SGLT-2i and epilepsy incidence.

Research Design and Methods: We emulated a target trail comparing SGLT-2i and dipeptidyl peptidase 4 inhibitors (DPP-4i) based on the Yinzhou Regional Health Care Database. Cohorts of T2DM patients who were new users of SGLT-2i or DPP-4i were assembled. Inverse probability of treatment weighting (IPTW) and Cox model were applied to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the association between use of SGLT-2i and incidence of epilepsy.

Results: The final cohort included 24930 new users of SGLT-2i and 28924 initiators of DPP-4i. A total of 243 incident epilepsy cases occurred during a median follow-up of 2.0 (IQR, 0.8~3.3) years, with the incidence of epilepsy being 174.2 and 231.5 per 100,000 person-years in users of SGLT-2i and DPP-4i, respectively. After controlling potential confounding using IPTW, SGLT-2i use was associated with a lower incidence of epilepsy, with an HR of 0.71 (95% CI, 0.52–0.97). Various subgroup analyses and sensitivity analyses supported the results in primary analyses.

Conclusions: SGLT-2i was associated with a reduced incidence of epilepsy in the study population. More studies are needed to confirm and replicate the study results.