Sodium-Glucose Cotransporter-2 Inhibitors and Arrhythmias: A Meta-Analysis of 38 Randomized Controlled Trials.

Summary

Across 38 RCTs including 88,704 patients, SGLT2 inhibitors reduced incident atrial arrhythmia (OR 0.85) and sudden cardiac death (OR 0.72) versus control, with no effect on ventricular arrhythmia or cardiac arrest. Benefits were observed over a mean 1.6-year follow-up.

Key Findings

• Across 38 RCTs (n=88,704), SGLT2i reduced incident atrial arrhythmia (OR 0.85, 95% CI 0.75-0.98, P=0.02).
• SGLT2i reduced sudden cardiac death (OR 0.72, 95% CI 0.55-0.94, P=0.02).
• No significant effect on ventricular arrhythmia (OR 1.03) or cardiac arrest (OR 0.94).
• Mean follow-up across trials was 1.6 years.

Clinical Implications

In patients with type 2 diabetes, heart failure, or CKD, SGLT2 inhibitors may be preferential when arrhythmic risk is a concern, while recognizing that ventricular arrhythmia risk is unchanged. Clinicians should not assume antiarrhythmic protection against ventricular events.

Limitations

• Arrhythmia and SCD were often secondary endpoints with heterogeneous ascertainment across trials.
• No individual patient data; limited ability to explore subgroup mechanisms or dose-response.

Future Directions

Individual patient-level meta-analyses and prospective, arrhythmia-focused RCTs are needed to confirm mechanisms, quantify AF burden reduction, and define subgroups with maximal benefit.