Sodium-glucose co-transporter 2 inhibitors and risk of post-stroke epilepsy

Stroke survivors may develop epilepsy, which can worsen recovery and quality of life. People with type 2 diabetes are at increased risk of both stroke and epilepsy, but whether different glucose-lowering medications influence the risk of post-stroke epilepsy (PSE) is unclear. We aimed to compare the risk of PSE between sodium–glucose cotransporter 2 inhibitors and dipeptidyl peptidase-4 inhibitors in people with type 2 diabetes after stroke. We conducted a retrospective cohort study using Taiwan’s National Health Insurance Research Database under a target trial emulation framework. We included 34,124 adults (age ≥18 years) with type 2 diabetes who had experienced a stroke and initiated either sodium–glucose cotransporter 2 inhibitors or dipeptidyl peptidase-4 inhibitors between 2016 and 2021. The primary outcome was post-stroke epilepsy or convulsive seizures. We compared risks between treatment groups using hazard ratios and performed subgroup analyses. We further assessed the robustness of the results using an independent electronic health record database. Here we show that treatment with sodium–glucose cotransporter 2 inhibitors is associated with a lower risk of PSE than treatment with dipeptidyl peptidase-4 inhibitors (hazard ratio, 0.56; 95% confidence interval, 0.44–0.71). Similar associations are observed across multiple patient subgroups and further supported by analyses using an independent electronic health record database. Our findings suggest that, among people with type 2 diabetes after stroke, treatment with sodium–glucose cotransporter 2 inhibitors is associated with a lower risk of developing PSE than treatment with dipeptidyl peptidase-4 inhibitors. These findings support further investigation of sodium–glucose cotransporter 2 inhibitors as a potential strategy to reduce the risk of PSE. Some people develop epilepsy after a stroke, which can make recovery more difficult. We investigated whether sodium–glucose cotransporter 2 inhibitors, a medicine used to treat type 2 diabetes, were associated with a lower risk of developing post-stroke epilepsy. We compared people with type 2 diabetes who had experienced a stroke and were treated with either sodium–glucose cotransporter 2 inhibitors or dipeptidyl peptidase-4 inhibitors. We found that people receiving sodium–glucose cotransporter 2 inhibitors had a lower risk of developing post-stroke epilepsy, and similar results were seen across different groups of patients. If confirmed in future studies, these findings may help doctors choose diabetes treatments that also reduce the risk of epilepsy after stroke. Chuang et al. estimate risk of post-stroke epilepsy (PSE) of sodium-glucose co-transporter 2 (SGLT2) inhibitors and dipeptidyl peptidase 4 (DPP4) inhibitors in type 2 diabetes patients with stroke. The study observes that SGLT2 inhibitors are associated with lower risk of PSE and suggests that SGLT2 inhibitors may offer neuroprotective benefits.