Antiarrhythmic effects of metformin

Atrial fibrillation/flutter (AF) is a major public health problem, associated with stroke, heart failure, dementia and death. It is estimated that 20-30% of Americans will develop AF at some point in their lifetime. 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 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 anti-arrhythmic 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 anti-arrhythmic mechanisms underlying this association. Repurposing a well-tolerated, safe, and inexpensive medication to prevent cardiac arrhythmias has significant positive public health implications.