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Open Access Highly Accessed Original investigation

Association of metformin with lower atrial fibrillation risk among patients with type 2 diabetes mellitus: a population-based dynamic cohort and in vitro studies

Shang-Hung Chang1, Lung-Sheng Wu1, Meng-Jiun Chiou2, Jia-Rou Liu2, Kuang-Hui Yu3, Chang-Fu Kuo3, Ming-Shien Wen1, Wei-Jan Chen1, Yung-Hsin Yeh1* and Lai-Chu See24*

Author Affiliations

1 Chang Gung University and Department of Cardiology, Chang Gung Memorial Hospital, Kweishan 333, Taoyuan, Taiwan

2 Department of Public Health, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan 333, Taoyuan, Taiwan

3 Department of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Kweishan 333, Taiwan

4 Biostatistics Core Laboratory, Molecular Medicine Research Center, Chang Gung University, Kweishan 333, Taiwan

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Cardiovascular Diabetology 2014, 13:123  doi:10.1186/s12933-014-0123-x

Published: 10 August 2014

Abstract

Background

Atrial fibrillation (AF), an inflammatory process involving arrhythmia, is associated with severe morbidity and mortality and commonly seen in patients with diabetes mellitus (DM). The effect of metformin, the most commonly used medication for patients with DM, on AF has not been investigated. The primary aim of this study was to examine whether metformin prevented the occurrence of AF in type 2 DM patients by analyzing a nationwide, population-based dynamic cohort. Additionally, we investigated the effect of metformin on tachycardia-induced myolysis and oxidative stress in atrial cells.

Methods

The study population included 645,710 patients with type 2 diabetes and not using other anti-diabetic medication from a subset of the Taiwan National Health Insurance Research Database. Of these patients, those who used metformin were categorized as the user group, and the remaining were classified as the non-user group. The time-dependent Cox’s proportional hazard model was used to examine the effect of metformin on AF and the status of metformin use was treated as a time-dependent covariate. HL-1 atrial cells were paced with or without metformin, and then troponin and heavy-chain-myosin were measured as markers of myolysis.

Results

After 13 years of follow-up, 9,983 patients developed AF with an incidence rate of 1.5% (287 per 100,000 person-years). After adjusting for co-morbidities and medications, metformin independently protected the diabetic patients from new-onset AF with a hazard ratio of .81 (95% confidence interval 0.76-0.86, p < 0.0001). Metformin significantly decreased the extent of pacing-induced myolysis and the production of reactive oxygen species.

Conclusion

Metformin use was associated with a decreased risk of AF in patients with type 2 DM who were not using other anti-diabetic medication, probably via attenuation of atrial cell tachycardia-induced myolysis and oxidative stress.

Keywords:
Metformin; Atrial fibrillation; Myolysis; Oxidative stress; Diabetes mellitus