Dissecting the reduction in cardiovascular death with SGLT2 inhibitors: Potential contribution of effects on ventricular arrhythmias and sudden cardiac death?

Type 2 diabetes is associated with a higher risk of cardiac arrhythmias, especially in presence of cardiovascular disease and/or heart failure. Ventricular arrhythmias (VA: tachycardia/fibrillation) may lead to sudden cardiac arrest/death (SCA/SCD). Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) exert a remarkable protection against cardiovascular disease, especially hospitalisation for heart failure, yet their effects on malignant cardiac arrhythmias are poorly known. Nevertheless, findings derived from experimental animal and clinical studies suggested that SGLT2is could reduce the risk of not only supraventricular but also ventricular cardiac arrhythmias. A trend for less VA and SCA/SCD events was reported in post hoc analyses of randomised controlled trials/cardiovascular outcome trials versus placebo, yet statistical significance was not reached presumably because of too few events in both treatment groups. Retrospective observational cohort studies that reported malignant cardiac arrhythmias in patients treated with SGLT2is versus other glucose-lowering agents are scare, compared to the numerous ones that focused on atrial fibrillation/flutter. Further studies specifically devoted to the effects of SGLT2is on malignant cardiac arrhythmias are needed to confirm positive effects in patients with diabetes and/or heart failure and if possible to carefully dissect the underlying anti-arrhythmic protective mechanisms.