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Review
. 2025 Sep 10;15(18):2288.
doi: 10.3390/diagnostics15182288.

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

Roopeessh Vempati  1 , Nanush Damarlapally  2 , Poulami Roy  3 , Maneeth Mylavarapu  4 , Srivatsa Surya Vasudevan  5 , Reshma Reguram  1 , Tanisha Vora  1 , Hritvik Jain  6 , Raheel Ahmed  7 , Geetha Krishnamoorthy  1
Affiliations
Review

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

Roopeessh Vempati et al. Diagnostics (Basel). .

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.

Keywords: atrial fibrillation; cardiovascular outcomes; meta-analysis; metformin; type 2 diabetes mellitus.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Study selection process of included studies.
Figure 2
Figure 2
Association of metformin with new-onset atrial fibrillation. Forest plot illustrating the association of metformin with new-onset atrial fibrillation outcomes [4,6,22,23,24,25,26].
Figure 3
Figure 3
Leave-one-out sensitivity analysis. Forest plot illustrating that no single study is exerting a disproportionate influence on the overall effect estimate [4,6,22,23,24,25,26].
Figure 4
Figure 4
Meta-regression analysis. Scatter plot illustrating meta-regression analysis of age as a factor.
Figure 5
Figure 5
Publication bias assessment. Funnel plot for publication bias assessment.
Figure 6
Figure 6
Risk of bias assessment of included studies. Traffic light plot for risk of bias assessment [4,6,22,23,24,25,26].
Figure 7
Figure 7
Metformin’s actions on atrial fibrillation. AGE/RAGE, Advanced Glycation End products/Receptor of Advanced Glycation End products; AMPK, AMP-activated Protein Kinase; ROS, Reactive Oxygen Species; PKC, Protein Kinase C; MAPK, Mitogen-Activated Protein Kinase.
See this image and copyright information in PMC

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