Effect of Sodium-Glucose Cotransporter 2 Inhibitors on the Prevention of Atrial Fibrillation and Its Complications: A Literature Review of Clinical Evidence and Translational Studies

Abstract Atrial fibrillation (AF) is one of the most commonly sustained cardiac arrhythmias, which increases the risk of ischemic stroke, heart failure, and death. Although great progress has been achieved in the treatment of AF, a proportion of patients are refractory to treatment with anti-arrhythmics or experience AF recurrence and progression. Accumulating evidence identifies diabetes mellitus (DM) as an independent risk factor for AF, indicating that glucose-lowering medications may be effective for the treatment of AF. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a relatively new class of anti-diabetes agents, may therefore offer an alternative therapeutic strategy for AF. While several reviews support the cardiovascular benefits of SGLT2i, few publications have specifically focused on their effects on AF. This review comprehensively summarizes existing clinical studies valuating the impact of SGLT2i on new-onset AF in DM patients without AF, AF recurrence risk in DM patients with AF, and associated poor prognosis. In addition, data derived from animal models exploring the influence of SGLT2i on the inducibility, incidence, and duration of AF, as well as the underlying molecular mechanisms, are summarized. The cumulative evidence suggests that the use of SGLT2i considerably reduces the risk of new-onset AF, AF recurrence, and AF-related complications. The potential underlying mechanisms involve regulation of ion exchange channels and energy metabolism, and inhibition of oxidative stress, mitochondrial dysfunction, inflammation, apoptosis, and fibrosis. Further studies should be carried out to verify these beneficial effects by integrating the studies with negative results and to further explore other mechanisms that explain the benefits of SGLT2i.