title: Association of metformin with lower atrial fibrillation risk among patients with type 2 diabetes mellitus: a population-based dynamic cohort and in vitro studies.
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.
  
  
  CONCLUSIONS
  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.
authors.forename: Shang-Hung
authors.initials: SH
authors.lastname: Chang
authors.forename: Lung-Sheng
authors.initials: LS
authors.lastname: Wu
authors.forename: Meng-Jiun
authors.initials: MJ
authors.lastname: Chiou
authors.forename: Jia-Rou
authors.initials: JR
authors.lastname: Liu
authors.forename: Kuang-Hui
authors.initials: KH
authors.lastname: Yu
authors.forename: Chang-Fu
authors.initials: CF
authors.lastname: Kuo
authors.forename: Ming-Shien
authors.initials: MS
authors.lastname: Wen
authors.forename: Wei-Jan
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: Chang Gung University and Department of Cardiology, Chang Gung Memorial Hospital, Kweishan 333, Taoyuan, Taiwan. yeongshinn@adm.cgmh.org.tw.
authors.forename: Yung-Hsin
authors.initials: YH
authors.lastname: Yeh
authors.forename: Lai-Chu
authors.initials: LC
authors.lastname: See
mesh_terms: D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000378:metabolism / Q000517:prevention & control*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods; D012307:Risk Factors
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
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