(C-005) Association between Sodium-Glucose Co-Transporter 2 Inhibitors and Risk of Post-Stroke Epilepsy

Background: Post-stroke epilepsy (PSE) is an important complication in stroke survivors, and diabetes is a known risk factor for both stroke and seizures. The role of antidiabetic drugs in post-stroke epilepsy remains unexplored.

Objectives: To estimate the risk of PSE of sodium-glucose co-transporter 2 (SGLT2) inhibitors and dipeptidyl peptidase 4 (DPP4) inhibitors in type 2 diabetes patients with stroke.

Methods: We conducted a retrospective cohort study using a target trial emulation framework, using data from global TriNetX platform. We included type 2 diabetes patients who treated SGLT2- or DPP4 inhibitors, and who were diagnosed with cerebrovascular events before initiation of the treatment. We defined the index date as initiation date of SGLT2 inhibitors or DPP4 inhibitors, with one-year wash-out period to exclude patients with prior exposure. The primary endpoints were incident seizure events, and epilepsy or recurrent seizure events, as identified from diagnosis records in electronic health records from TriNetX platform. We calculated hazard ratios (HR) to compare relative risks of post-stroke epilepsy of SGLT2 inhibitors, using DPP4 inhibitors as the reference group. We implemented several subgroup analyses using age, sex, insulin use, glycemic control and renal function to test our findings’ robustness. We also conducted sensitivity analyses by applying per-protocol effects and negative control outcome.

Results: Among 37,337 patients, we found SGLT2 inhibitors were associated with a lower risk of PSE, compared to DPP4 inhibitors (HR: 0.75; 95% CI: 0.67-0.84). We also observed an association between SGLT2 inhibitors and a lower risk of PSE in several subgroup- and sensitivity analyses. We found no significant difference between SGLT2- or DPP4 inhibitors in the negative control outcomes.

Conclusions: Our retrospective cohort study utilizing global electronic health records indicated that patients with type 2 diabetes who use SGLT2 inhibitors have a lower risk of developing post-stroke epilepsy, compared to those using DPP4 inhibitors. This association was particularly pronounced in individuals over 65 years old and those with poor glycemic control. Overall, our study provided evidence that SGLT2 inhibitors may offer protective benefits against post-stroke epilepsy in patients with type 2 diabetes.