Metformin and Risk of New-Onset Atrial Fibrillation in Type 2 Diabetes: A Systematic Review and Meta-Analysis

Abstract

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, increasingly prevalent worldwide. Type 2 diabetes mellitus (T2DM) is a major chronic disorder and a significant risk factor for AF, contributing to high morbidity and mortality. Metformin monotherapy can contribute to the reduced occurrence of adverse cardiovascular outcomes in patients with T2DM, but its effects on AF are understudied. This meta-analysis evaluates the association of metformin with the risk of incident AF among patients with T2DM on metformin. Methods: Databases, including PubMed, Google Scholar, and EMBASE, were screened through November 2024 for studies evaluating the association between metformin and new-onset AF in patients with T2DM. Comprehensive Meta-Analysis (CMA) version 4, by Biostat, Inc., utilizing a random effects model, was used to pool hazard ratios (HR) and 95% confidence intervals (CI). A meta-regression analysis was also performed to identify factors that may have influenced the results. A p-value < 0.05 was considered statistically significant. Results: A total of seven studies, comprising 4,017,929 patients with T2DM, having a mean age of 62.82 years and 52.5% males, were included. Metformin was associated with a statistically significantly lower risk of new-onset AF among patients with T2DM compared to other hypoglycemic agents (aHR: 0.85; 95% CI 0.76–0.94; p = 0.002). Meta-regression analysis identified age as a significant moderator of the treatment effect (β = −3.15, p = 0.001). Conclusions: Metformin is associated with a lower risk of new-onset AF among patients with T2DM compared to other hypoglycemic agents. Furthermore, age-related attenuation of this association was observed, with older patients with T2DM showing a weaker association.