Anti-Arrhythmic Effects of Sodium-Glucose Co-Transporter 2 Inhibitors

Abstract

Arrhythmias are clinically prevalent with a high mortality rate. They impose a huge economic burden, thereby substantially affecting the quality of life. Sodium-glucose co-transporter 2 inhibitor (SGLT2i) is a new type of hypoglycemic drug, which can regulate blood glucose level safely and effectively. Additionally, it reduces the occurrence and progression of heart failure and cardiovascular events significantly. Recently, studies have found that SGLT2i can alleviate the occurrence and progression of cardiac arrhythmias; however, the exact mechanism remains unclear. In this review, we aimed to discuss and summarize new literature on different modes in which SGLT2i ameliorates the occurrence and development of cardiac arrhythmias.

Keywords: SGLT2I; arrhythmia; cardiac electrical remodeling; cardiac structural remodeling; inflammation; mitochondrial dysfunction; oxidative stress.

FIGURE 1

Mechanisms of SGLT2is′ effect on arrhythmias. Red lines represent the effect of SGLT2i; black lines mean mechanisms of arrhythmias. (1)SGLT2is can affect cardiomyocytes’ electrical remodeling, including inhibiting I _Na-Late, NHE,Ca ²⁺ spark, the decreasing of ATP, RYR2 phosphorylation, CaMKII activity, inflammatory cytokines; increasing Ito, IK, SERCA2a activity, so that intracellular Na ⁺ and Ca ²⁺ overload and the disorder of K ⁺ currents could be ameliorated. (2)SGLT2is can ameliorate arrhythmias by inhibiting myocardial inflammation and structural remodeling, including inhibiting NLRP3, inflammatory cytokines and fibrosis, so that K ⁺ currents’ disorder can be improved. (3)SGLT2is can ameliorate arrhythmias by improving mitochondrial dysfunction and oxidative stress, including promoting mitochondrial biogenesis; inhibiting the decreasing of ATP, the increasing of ROS, so that intracellular ions administration can be improved. (4)SGLT2is can ameliorate arrhythmias by ameliorating autophagy.