Effect of SGLT2 inhibitors on arrhythmic and device-therapy outcomes in heart failure patients with ICD/CRT-D: a systematic review and meta-analysis

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve heart failure outcomes, but their association with arrhythmic events and device-therapy endpoints in patients with implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy-defibrillator (CRT-D) devices remains uncertain. Methods This systematic review and meta-analysis followed PRISMA 2020 guidance and was registered in PROSPERO (CRD420261299813). We searched PubMed, PubMed Central, Google Scholar, and ScienceDirect through 01 March 2026 for studies of adults with heart failure and an ICD/CRT-D, or device-based rhythm monitoring, who received an SGLT2 inhibitor versus placebo, standard therapy, or no SGLT2i. Random-effects meta-analysis (DerSimonian-Laird estimator, log risk-ratio scale) was performed for any arrhythmia events and ICD therapy events, with leave-one-out and study-design-stratified sensitivity analyses. Risk of bias was assessed with RoB 2 and ROBINS-I, and certainty of evidence with GRADE. Results We identified 169 records and included 8 studies in the review. Five studies contributed to the any arrhythmia events meta-analysis; SGLT2i therapy was associated with a non-significant reduction (RR 0.82, 95% CI 0.53 to 1.25, p = 0.3485; I2 = 62.5%), a result that stayed non-significant across leave-one-out and study-design-stratified analyses (RR range 0.69–0.92). Four studies contributed to ICD therapy events, where SGLT2i therapy was associated with a significant reduction (RR 0.53, 95% CI 0.38 to 0.74, p = 0.0002; I2 = 0.0%) that held when restricted to randomized trials (RR 0.59, 95% CI 0.37 to 0.94) and when the single before-after study was excluded (RR 0.52, 95% CI 0.36 to 0.73). Conclusion SGLT2i therapy was associated with a significant, design-consistent reduction in ICD therapy events, though this evidence remains low-certainty given the small number of contributing studies, the inclusion of a before-after design, and inconsistent definitions of ICD therapy across studies. The broader any arrhythmia outcome remained non-significant and uncertain. We interpret these findings as a hypothesis-generating signal of a possible reduction in device-treated arrhythmic events, not an established treatment effect, and larger, standardized, device-focused studies are still needed.