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Drug Safety

, Volume 36, Issue 8, pp 643–649 | Cite as

Risk of Bladder Cancer in Diabetic Patients Treated with Rosiglitazone or Pioglitazone: A Nested Case–Control Study

  • Fei-Yuan HsiaoEmail author
  • Pei-Hua Hsieh
  • Weng-Foung Huang
  • Yi-Wen Tsai
  • Churn-Shiouh GauEmail author
Original Research Article

Abstract

Background

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.

Objective

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.

Methods

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.

Results

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]).

Conclusions

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.

Keywords

Chronic Obstructive Pulmonary Disease Bladder Cancer Rosiglitazone Pioglitazone Index Date 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

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.

Author contributions

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.

Financial support

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.

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Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  1. 1.Graduate Institute of Clinical Pharmacy, College of MedicineNational Taiwan UniversityTaipeiTaiwan
  2. 2.Institute of Health and Welfare PolicyNational Yang-Ming UniversityTaipeiTaiwan
  3. 3.Center for Drug EvaluationTaipeiTaiwan
  4. 4.Food and Drug Administration, Department of HealthExecutive YuanTaiwan

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