Sex Differences in Antiarrhythmic Effects of Empagliflozin: The EMPA-ICD Trial Subanalysis

The EMPA-ICD (Empagliflozin in Patients with Type 2 Diabetes Treated with an Implantable Cardioverter-Defibrillator; jRCTs031180120) trial is a prospective, multicenter, randomized, double-blind, placebo-controlled study evaluating the effects of empagliflozin on ventricular arrhythmias (VAs) in patients with type 2 diabetes (T2DM) treated with implantable cardioverter-defibrillators (ICDs). The trial showed that empagliflozin reduces VAs, but whether this effect differs by sex remains unclear.

This EMPA-ICD trial subanalysis aimed to assess sex-specific differences in the antiarrhythmic effects of empagliflozin in ICD-treated patients with T2DM.

The primary endpoint was the change in the number of VAs, including nonsustained ventricular tachycardia, sustained ventricular tachycardia, and ventricular fibrillation, detected by the ICDs over 24 weeks.

Between April 2019 and April 2021, a total of 150 patients were randomized to receive either empagliflozin or placebo at 31 centers in Japan. In men, the rate of ventricular arrhythmia events was significantly lower in the empagliflozin group than in the placebo group, with a rate ratio of 0.33 (95% CI: 0.27-0.39; P < 0.001). In women, the rate ratio was 1.78 (95% CI: 0.54-5.90; P = 0.35), with no statistically significant difference observed. Notably, a significant interaction between sex and treatment was observed, suggesting a sex-specific treatment response (P = 0.006) CONCLUSIONS: The arrhythmic effect of empagliflozin in patients with T2DM treated with ICDs appears to be more pronounced in men than in women. These findings underscore the need for investigating sex-specific responses to sodium-glucose cotransporter 2 inhibitors, advancing personalized strategies for arrhythmia management.