Risk of Bladder Cancer in Diabetic Patients Treated with Rosiglitazone or Pioglitazone: A Nested Case–Control Study
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Evidence has emerged that pioglitazone may increase the risk of bladder cancer, but the association has not been confirmed. This potential risk also has not been evaluated in users of rosiglitazone.
Using Taiwan’s National Health Insurance Research Database (NHIRD), this large population-based nested case–control study was conducted to explore the relationship between the use of rosiglitazone or pioglitazone and risk of bladder cancer in diabetic patients.
We identified 3,412 cases of newly diagnosed bladder cancer and 17,060 controls (1:5 matched by age and sex) among a diabetic patient cohort from the NHIRD. We defined an index date for each case as the date of first hospitalization for bladder cancer. Each control was assigned the index date of their corresponding case. Multivariable conditional logistic regressions were used to estimate the association between exposure (timing and duration) to rosiglitazone or pioglitazone and bladder cancer. We defined rosiglitazone or pioglitazone exposure as “current” if the prescription duration covered the index date or ended at 90 days before, as “recent” if it ended 91–180 days before the index date, or as “past” if the last prescription ended more than 180 days before. Duration of rosiglitazone or pioglitazone use was defined based on the cumulative days of exposure prior to the index date: <1, 1–2 and ≥2 years.
Rosiglitazone and pioglitazone use were associated with risk of bladder cancer and the associations were stronger with a longer term of exposure (pioglitazone <1 year odds ratio [OR] 1.45 [95 % CI 1.12–1.87, p < 0.01], 1–2 years OR 1.74 [95 % CI 1.05–2.90, p = 0.03] and ≥2 years OR 2.93 [95 % CI 1.59–5.38, p < 0.01]; rosiglitazone <1 year OR 0.98 [95 % CI 0.82–1.17, p = 0.81], 1–2 years OR 1.78 [95 % CI 1.31–2.39, p < 0.01] and ≥2 years OR 2.00 [95 % CI 1.37–2.92, p < 0.01]).
Long-term exposures to pioglitazone and rosiglitazone were associated with higher odds of bladder cancer, and the highest odds were seen in users with ≥2 years of exposure.
KeywordsChronic Obstructive Pulmonary Disease Bladder Cancer Rosiglitazone Pioglitazone Index Date
We thank the Bureau of National Health Insurance (BNHI) and National Health Research Institutes (NHRI) for making available the databases for this study. The content of this article, however, in no way represents any official position of the BNHI or NHRI. The authors bear all responsibility for the results and interpretation of the results. We thank Dr. C. Daniel Mullins of the University of Maryland and Dr. Susan Shur-Fen Gau of the National Taiwan University for providing consultation and assistance with the revised manuscript.
Dr F.Y. Hsiao, Ms P.H. Hsieh and Dr C.S. Gau were responsible for development of the study concept and design and the preparation of the manuscript. Dr F.Y. Hsiao and Ms P.H. Hsieh contributed to data acquisition and statistical analysis. All authors participated in the analysis and interpretation of the data of the manuscript. This manuscript has been read and approved by all authors.
No sources of funding were used to conduct this study or prepare this manuscript.
Conflict of interest
Pei-Hua Hsieh received a part-time research assistantship from a research project (DOH100-FDA-41100) sponsored by the Food and Drug Administration, Taiwan. Fei-Yuan Hsiao, Weng-Foung Huang, Yi-Wen Tsai and Churn-Shiouh Gau have no conflicts of interest to declare that are directly relevant to the content of this study.
- 2.Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366(9493):1279–89.PubMedCrossRefGoogle Scholar
- 9.Centers for Disease Control and Prevention. International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM). http://www.cdc.gov/nchs/icd/icd9cm.htm (Accessed 15 March 2013).
- 10.Hsiao FY, Yang CL, Huang YT, Huang WF. Using Taiwan’s national health insurance research databases for pharmacoepidemiology research. J Food Drug Anal. 2007;15(2):99–108.Google Scholar
- 19.Burea of National Health Insurance, Taiwan. Special medical needs: catastrophic illness patients. http://www.nhi.gov.tw/English/webdata/webdata.aspx?menu=11&menu_id=596&WD_ID=596&webdata_id=3180 (Accessed 15 May 2012).