Antiarrhythmic effects of metformin.

Atrial fibrillation/flutter (AF) is a major public health problem and is associated with stroke, heart failure, dementia, and death. It is estimated that 20%-30% of Americans will develop AF at some point in their life. Current medications to prevent AF have limited efficacy and significant adverse effects. Newer and safer therapies to prevent AF are needed. Ventricular arrhythmias are less prevalent than AF but may have significant consequences including sudden cardiac death. Metformin is the most prescribed, first-line medication for treatment of diabetes mellitus (DM). It decreases hepatic glucose production but also reduces inflammation and oxidative stress. Experimental studies have shown that metformin improves metabolic, electrical, and histologic risk factors associated with AF and ventricular arrhythmias. Furthermore, in large clinical observational studies, metformin has been associated with a reduced risk of AF in people with DM. These data suggest that metformin may have antiarrhythmic properties and may be a candidate to be repurposed as a medication to prevent cardiac arrhythmias. In this article, we review the clinical observational and experimental evidence for the association between metformin and cardiac arrhythmias. We also discuss the potential antiarrhythmic mechanisms underlying this association. Repurposing a well-tolerated, safe, and inexpensive medication to prevent cardiac arrhythmias has significant positive public health implications.