Sodium-glucose Cotransporter Type 2 Inhibitors and Cardiac Arrhythmias

The introduction of sodium-glucose cotransporter 2 (SGLT2) inhibitors as a new and effective class of therapeutic agents for type 2 diabetes (T2D) preventing the reabsorption of glucose in the kidneys and thus facilitating glucose excretion in the urine, but also as agents with cardiovascular benefits, particularly in patients with heart failure (HF), regardless of the diabetic status, has ushered in a new era in treating patients with T2D and/or HF. In addition, data have recently emerged indicating an antiarrhythmic effect of the SGLT2 inhibitors in patients with and without diabetes. Prospective studies, randomized controlled trials and meta-analyses have provided robust evidence for a protective and beneficial effect of these agents against atrial fibrillation, ventricular arrhythmias and sudden cardiac death. The antiarrhythmic mechanisms involved include reverse atrial and ventricular remodeling, amelioration of mitochondrial function, reduction of hypoglycemic episodes with their attendant arrhythmogenic effects, attenuated sympathetic nervous system activity, regulation of sodium and calcium homeostasis, and suppression of prolonged ventricular repolarization. These new data on antiarrhythmic actions of SGLT2 inhibitors are herein reviewed, potential mechanisms involved are discussed and pictorially illustrated, and treatment results on specific arrhythmias are described and tabulated. (c) 2022 Elsevier Inc. All rights reserved.