Introduction and Objective: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are widely used for type 2 diabetes and reduce hospitalization and cardiovascular death in heart failure with reduced ejection fraction (HFrEF). Ventricular arrhythmias are a major cause of death in HFrEF, but the effect of SGLT2i on arrhythmia risk remains unclear. This systematic review and meta-analysis evaluated whether SGLT2i modulate arrhythmia risk beyond their established cardioprotective effects.Objective-To assess whether SGLT2i reduce serious cardiac arrhythmias and sudden death in high-risk cardiovascular patients. Methods: We performed a systematic review and meta-analysis of RCTs comparing SGLT2i with placebo. PubMed, Cochrane, Embase, and Web of Science were searched. Eight RCTs conducted between 2019-2025 (DAPA-HF, CREDENCE, DELIVER, DETAIL-CMIV, EMPA-ICD, EMPACT-MI, EMPEROR-Preserved, SOLOIST-WHF) including ~29,500 patients (mean age 63-72, median follow-up 0.75-2.6 years) were analyzed. Results: Eight RCTs (n≈16,000 with HF/T2DM/CKD) showed significant arrhythmia benefits. Dapagliflozin reduced serious ventricular arrhythmia/sudden death by 21% (HR 0.79, 95% CI 0.63-0.99, p=0.037). Empagliflozin reduced device-recorded VT/VF/NSVT (p0.001). Pooled analysis of four trials showed tachycardia incidence trended 10% lower (RR 0.90, 95% CI 0.76-1.05, p=0.19, I²=0%), supraventricular tachycardia was unchanged (RR 0.95, 95% CI 0.77-1.16, p=0.60), and cardiac arrest was reduced in CKD (RR 0.50, 95% CI 0.26-0.95, p=0.03). Benefits were consistent across EF categories and baseline arrhythmia status, with no heterogeneity. Conclusion: Although reductions in arrhythmia burden did not reach statistical significance, the consistent trend, absence of heterogeneity, and lack of publication bias suggest SGLT2i have a favorable electrophysiological safety profile and may offer additional arrhythmic protection in high-risk cardiovascular populations. Disclosure U.S. Akkala Shetty: None.
UDAY S. AKKALA SHETTY (Mon,) studied this question.