Thiazolidinedione and reduced epilepsy risk: A population-based study using target trial emulation

OBJECTIVE: No epidemiological studies have yet explored the relationship between TZD use and epilepsy incidence within a population context. This study aimed to evaluate the association between TZD use and risk of epilepsy in a Chinese population by using a target trial emulation framework with active-comparator new-user (ACNU) design. METHODS: We emulated a target trial comparing the risk of epilepsy between use of TZDs and alpha glucosidase inhibitors (AGIs) in patients with type 2 diabetes mellitus (T2DM). Participants aged between 18 and 100 years, who were new users of TZDs or AGIs were included. The primary outcome was incident epilepsy identified by using ICD-10 codes. A Cox model with inverse probability of treatment weighting (IPTW) was used to estimate the hazard ratio (HR) and confidence interval (CI). Various subgroup analyses and sensitivity analyses were conducted. RESULTS: The final cohort included 22,128 new users of TZDs and 79,166 new users of AGIs. The mean age was 60.3 (SD, 12.8) years and 47.2% of participants were female. The incidence of epilepsy was 140.1 per 100,000 person-years in users of TZDs and 208.2 per 100,000 person-years for AGIs users, respectively. After adjusting for potential confounders using stabilized IPTW, use of TZDs was associated with a 23% (HR 0.77; 95% CI, 0.64-0.93) decrease in incidence of epilepsy. This association was consistent in various subgroup analyses and sensitivity analyses. CONCLUSION: Our results indicated that use of TZDs was associated with reduced risk of epilepsy in the study population. More studies are needed to confirm and replicate the study results in other settings and populations..