Potential roles of sodium-glucose co-transporter 2 inhibitors in attenuating cardiac arrhythmias in diabetes and heart failure

Abstract

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are antidiabetic drugs that have been shown to exert cardiovascular benefits. Their benefits including a reduction of cardiovascular events and worsening heart failure have been extended to nondiabetic patients with high-risk. Although both heart failure and diabetes are known to increase risk of cardiac arrhythmias, the effects of SGLT-2 inhibitors on arrhythmia reduction and their underlying mechanisms are still not fully understood. This review aims to summarize the current available evidence ranging from basic research to clinical reports regarding the potential benefits of SGLT-2 inhibitors against cardiac arrhythmias. Previous in vitro and in vivo studies using various models including heart failure and diabetes are comprehensively summarized to examine the evidence of how SGLT-2 inhibitors affect cardiac action potential, cellular ion currents, calcium ion homeostasis, and cardiac mitochondrial function. Clinical reports investigating the association between SGLT-2 inhibitors and arrhythmias including atrial fibrillation and ventricular arrhythmias are also comprehensively summarized. Valuable information obtained from this review can be used to encourage further clinical investigations to warrant the potential use of SGLT-2 inhibitors against cardiac arrhythmias in both diabetic and heart failure settings.

Keywords: arrhythmia; diabetes mellitus; heart failure; ion channels; sodium-glucose transporter 2 inhibitors.