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Metformin may reduce bladder cancer risk in Taiwanese patients with type 2 diabetes

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Abstract

Whether metformin therapy affects bladder cancer risk in patients with type 2 diabetes mellitus (T2DM) has not been extensively investigated. The reimbursement databases of all Taiwanese patients with a new diagnosis of T2DM between 1998 and 2002 (n = 940,708) were retrieved from the National Health Insurance for follow-up of bladder cancer up to the end of 2009. Metformin was treated as a time-dependent variable, and of these patients, 532,519 were never-users and 408,189 were ever-users of metformin. A time-dependent approach was applied in the calculation of bladder cancer incidence and in the estimation of hazard ratios by Cox regression for ever-users, never-users, and subgroups of metformin exposure (using tertile cutoffs of cumulative duration of therapy and cumulative dose). During the study period, 1,847 (0.45 %) metformin ever-users and 6,213 (1.17 %) metformin never-users developed bladder cancer, representing an incidence of 72.03 and 189.22 per 100,000 person-years, respectively. The age-sex-adjusted and multivariable-adjusted hazard ratios (95 % confidence intervals) for ever- versus never-users were 0.382 (0.360–0.405) and 0.600 (0.564–0.638), respectively. The multivariable-adjusted hazard ratios for the first, second, and third tertiles of cumulative duration of metformin therapy were 1.034 (0.954–1.120), 0.696 (0.632–0.766), and 0.258 (0.229–0.291), respectively (P trend <0.0001). Similarly, the multivariable-adjusted hazard ratios for the first, second, and third tertiles of cumulative dose of metformin were 0.997 (0.920–1.080), 0.615 (0.559–0.677), and 0.285 (0.253–0.321), respectively (P trend <0.0001). This study suggests that metformin use is associated with a decreased risk of bladder cancer in patients with T2DM.

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Acknowledgments

The study was supported by the National Science Council (NSC102-2314-B-002-067) of Taiwan. It is based in part on data from the National Health Insurance Research Database provided by the Bureau of National Health Insurance, Department of Health and managed by National Health Research Institutes (Registered number 99274). The interpretation and conclusions contained herein do not represent those of Bureau of National Health Insurance, Department of Health or National Health Research Institutes. The excellent help in statistical analyses by Ting–Ting Chang was highly appreciated.

Conflict of interest

None.

Human and Animal Rights

The study was conducted according to local regulations.

Informed Consent

The identification information of the persons has been scrambled and handled by the National Health Research Institutes. No indentifying details are available in the databases provided for statistical analyses and personal information is not shown in the manuscript.

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Authors and Affiliations

  1. Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

    Chin-Hsiao Tseng

  2. Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

    Chin-Hsiao Tseng

  3. Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Taipei, Taiwan

    Chin-Hsiao Tseng

  4. Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei, 100, Taiwan

    Chin-Hsiao Tseng

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  1. Chin-Hsiao Tseng
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Correspondence to Chin-Hsiao Tseng.

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Communicated by Massimo Porta.

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Tseng, CH. Metformin may reduce bladder cancer risk in Taiwanese patients with type 2 diabetes. Acta Diabetol 51, 295–303 (2014). https://doi.org/10.1007/s00592-014-0562-6

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  • DOI: https://doi.org/10.1007/s00592-014-0562-6

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