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Metformin versus sulphonylureas for new onset atrial fibrillation and stroke in type 2 diabetes mellitus: a population-based study

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Abstract

Aims

To gain insights on the cardiovascular effects of metformin and sulphonylurea, the present study compares the rates of incident atrial fibrillation, stroke, cardiovascular mortality and all-cause mortality between metformin and sulphonylurea users in type 2 diabetes mellitus.

Methods

This was a retrospective population-based cohort study of type 2 diabetes mellitus patients receiving either sulphonylurea or metformin monotherapy between January 1, 2000, and December 31, 2019. The primary outcome was new-onset AF or stroke. Secondary outcomes were cardiovascular, non-cardiovascular and all-cause mortality. Propensity score matching (1:2 ratio) between sulphonylurea and metformin users was performed, based on demographics, CHA-DS-VASc score, past comorbidities and medication use. Cox regression was used to identify significant risk factors. Competing risk analysis was conducted using cause-specific and subdistribution hazard models. Sensitivity analyses using propensity score stratification, high-dimensional propensity score and inverse probability of treatment weighting were conducted. Subgroup analyses were conducted for age and gender in the matched cohort.

Results

A total of 36,228 sulphonylurea users and 72,456 metformin users were included in the propensity score-matched cohort. Multivariable Cox regression showed that sulphonylurea users had higher risks of incident AF (hazard ratio [HR]: 2.89, 95% confidence interval [CI]: 2.75–3.77; P < 0.0001), stroke (HR: 3.23, 95% CI: 3.01–3.45; P < 0.0001), cardiovascular mortality (HR: 3.60, 95% CI: 2.62–4.81; P < 0.0001) and all-cause mortality (HR: 4.35, 95% CI: 3.16–4.75; P < 0.0001) compared to metformin users. Similarly, significant results were observed using cause-specific and subdistribution hazard models. Sensitivity analysis using techniques based on the propensity score also yielded similar results.

Conclusions

Sulphonylurea use was associated with higher risks of incident AF, stroke, cardiovascular mortality and all-cause mortality compared to metformin. Males and patients older than 65 years with sulphonylurea use were exposed to the highest risks.

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Data availability

The data will be available upon requests to the corresponding authors.

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Funding

There is no funding for this project to declare.

Author information

Author notes

  1. Jiandong Zhou, Guoming Zhang equal contributions as joint first authors.

Authors and Affiliations

  1. Nuffield Department of Medicine, University of Oxford, Oxford, UK

    Jiandong Zhou

  2. Emergency Department, Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, Fujian, China

    Guoming Zhang

  3. Department of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China

    Carlin Chang & Oscar Hou In Chou

  4. Diabetes Research Unit, Cardiovascular Analytics Group, UK-China Collaboration, Hong Kong, China

    Oscar Hou In Chou & Sharen Lee

  5. Aston Medical School, Aston University, Birmingham, UK

    Keith Sai Kit Leung

  6. Emergency Medicine Unit, Li Ka Shing, Faculty of Medicine, The University of Hong Kong, Hong Kong, China

    Keith Sai Kit Leung & Abraham Ka Chung Wai

  7. School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China

    Wing Tak Wong

  8. Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, 300211, China

    Tong Liu & Gary Tse

  9. School of Biomedical Sciences, City University of Hong Kong, Hong Kong, China

    Shuk Han Cheng

  10. School of Data Science, City University of Hong Kong, Kowloon City, Hong Kong, China

    Qingpeng Zhang

  11. Kent and Medway Medical School, Canterbury, UK

    Gary Tse

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  1. Jiandong Zhou
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Contributions

JD, GZ, CC and OHIC carried out data analysis, data interpretation, statistical analysis, manuscript drafting and critical revision of manuscript. SL, KSKL, WTW, TL, AKCW and SHC were involved in project planning, data acquisition, data interpretation and critical revision of manuscript. QZ and GT took part in study conception, study supervision, project planning, data interpretation, statistical analysis, manuscript drafting and critical revision of manuscript.

Corresponding authors

Correspondence to Qingpeng Zhang or Gary Tse.

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The authors have no conflicts of interest to declare.

Ethical approval

This retrospective population-based cohort study received approval from the Joint Chinese University of Hong Kong—New Territories East Cluster Clinical Research Ethics Committee.

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Zhou, J., Zhang, G., Chang, C. et al. Metformin versus sulphonylureas for new onset atrial fibrillation and stroke in type 2 diabetes mellitus: a population-based study. Acta Diabetol 59, 697–709 (2022). https://doi.org/10.1007/s00592-021-01841-4

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  • DOI: https://doi.org/10.1007/s00592-021-01841-4

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