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

Fu-Shun Yen1, Yu-Hsin Yen2, Yao-Min Hung3,4,5,6

  • 1Dr. Yen's Clinic, Taoyuan, Taiwan.

Epilepsia
|July 3, 2026
PubMed
Abstract

Insights

Patients with type 2 diabetes (T2D) on sodium-glucose cotransporter-2 inhibitors (SGLT2is) had lower seizure and epilepsy risks versus DPP-4 inhibitors. SGLT2i use also showed reduced composite seizure/epilepsy risk compared to GLP-1 RAs.

Area of Science:

  • Endocrinology
  • Neurology
  • Pharmacology

Background:

  • Type 2 diabetes (T2D) management involves various drug classes.
  • Seizures and epilepsy are potential comorbidities or adverse events in T2D patients.
  • Comparative risk data for neurological outcomes among different T2D medications are limited.

Purpose of the Study:

  • To compare the risk of seizures and epilepsy in T2D patients initiating SGLT2 inhibitors (SGLT2is), GLP-1 receptor agonists (GLP-1 RAs), or DPP-4 inhibitors.
  • To utilize nationwide real-world data for robust comparative analysis.

Main Methods:

  • Propensity score matching was employed to create comparable cohorts.
  • Large-scale data from the Taiwanese National Health Insurance Research Database (2000-2021) were analyzed.
  • Cox proportional hazards models assessed outcome risks between treatment groups.

Main Results:

  • SGLT2i users exhibited significantly lower cumulative incidences of seizure, epilepsy, and a composite outcome compared to DPP-4 inhibitor users (aHRs ranging from 0.38 to 0.49).
  • SGLT2i users showed a lower risk of the composite outcome versus GLP-1 RA users (aHR=0.66), but not for individual seizure or epilepsy events.
  • No significant differences in seizure or epilepsy risk were observed between GLP-1 RAs and DPP-4 inhibitors.

Conclusions:

  • Sodium-glucose cotransporter-2 inhibitor (SGLT2i) use in T2D patients is associated with reduced risks of seizure and epilepsy compared to dipeptidyl peptidase-4 (DPP-4) inhibitors.
  • SGLT2i use demonstrated a lower composite risk of seizure/epilepsy compared to glucagon-like peptide-1 receptor agonists (GLP-1 RAs).
  • Findings suggest a potential neuroprotective association with SGLT2i therapy in T2D management.
Keywords:
DPP‐4 inhibitorsepilepsyglucagonlike peptide‐1 receptor agonistsseizuresodium‐glucose cotransporter‐2 inhibitors

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