Evidence map›Paper›PMID 25106079›Full record

ArticleCardiovascular diabetology2014

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 Chang, Lung-Sheng Wu, Meng-Jiun Chiou, Jia-Rou Liu, Kuang-Hui Yu, Chang-Fu Kuo, Ming-Shien Wen, Wei-Jan Chen, Yung-Hsin Yeh, Lai-Chu See

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PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular diabetology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed, 4 pooled it
6.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

109 citing papers in PubMed, 4 syntheses or guidelines pooled it, 230 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. European Heart Rhythm Association (EHRA)/European Association of Cardiovascular Prevention and Rehabilitation (EACPR) position paper on how to prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) and Asia Pacific Heart Rhythm Society (APHRS).Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2017
    Guideline
  4. Guideline
  5. Article
  6. Modifiable Risk Factors in Atrial Fibrillation: Clinical Implications and Pathophysiological Insights.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2026
    Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Metformin Protects Against Persistent Atrial Fibrillation in an Equine Model.Circulation. Arrhythmia and electrophysiology · 2025
    Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Review
  18. Review
  19. Upstream targeting for the prevention of atrial fibrillation: Targeting Risk Interventions and Metformin for Atrial Fibrillation (TRIM-AF)-rationale and study design.Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing · 2025
    Article
  20. Review

49 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Shang-Hung Chang
Lung-Sheng Wu
Meng-Jiun Chiou
Jia-Rou Liu
Kuang-Hui Yu
Chang-Fu Kuo
Ming-Shien Wen
Wei-Jan Chen
Yung-Hsin YehChang Gung University and Department of Cardiology, Chang Gung Memorial Hospital, Kweishan 333, Taoyuan, Taiwan. yeongshinn@adm.cgmh.org.tw.
Lai-Chu See
Chang Gung Memorial Hospital · TWChang Gung University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAtrial 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.

methodsThe 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.

resultsAfter 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.

conclusionMetformin 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.

Indexed as

Population SurveillanceAdultAgedAtrial FibrillationCohort StudiesDiabetes Mellitus, Type 2FemaleFollow-Up StudiesHumansHypoglycemic AgentsLongitudinal StudiesMaleMetforminMiddle AgedRisk FactorsHypoglycemic AgentsMetformin

Identifiers

PMID25106079
PMCPMC4149273
OpenAlexW2150052417

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.