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The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case-control study

BMJ 2012; 344 doi: (Published 31 May 2012) Cite this as: BMJ 2012;344:e3645
  1. Laurent Azoulay, assistant professor12,
  2. Hui Yin, statistician1,
  3. Kristian B Filion, assistant professor13,
  4. Jonathan Assayag, graduate student1,
  5. Agnieszka Majdan, endocrinologist4,
  6. Michael N Pollak, oncologist and professor2,
  7. Samy Suissa, professor5
  1. 1Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Côte Sainte-Catherine, H-425.1, Montreal, Quebec, Canada, H3T 1E2
  2. 2Department of Oncology, McGill University, Montreal, Quebec, Canada
  3. 3Division of Clinical Epidemiology, McGill University, Montreal
  4. 4Division of Endocrinology, Jewish General Hospital, Montreal
  5. 5Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal
  1. Correspondence to: L Azoulay laurent.azoulay{at}
  • Accepted 18 April 2012


Objective To determine if the use of pioglitazone is associated with an increased risk of incident bladder cancer in people with type 2 diabetes.

Design Retrospective cohort study using a nested case-control analysis.

Setting Over 600 general practices in the United Kingdom contributing to the general practice research database.

Participants The cohort consisted of people with type 2 diabetes who were newly treated with oral hypoglycaemic agents between 1 January 1988 and 31 December 2009. All incident cases of bladder cancer occurring during follow-up were identified and matched to up to 20 controls on year of birth, year of cohort entry, sex, and duration of follow-up. Exposure was defined as ever use of pioglitazone, along with measures of duration and cumulative dosage.

Main outcome measure Risk of incident bladder cancer associated with use of pioglitazone.

Results The cohort included 115 727 new users of oral hypoglycaemic agents, with 470 patients diagnosed as having bladder cancer during follow-up (rate 89.4 per 100 000 person years). The 376 cases of bladder cancer that were diagnosed beyond one year of follow-up were matched to 6699 controls. Overall, ever use of pioglitazone was associated with an increased rate of bladder cancer (rate ratio 1.83, 95% confidence interval 1.10 to 3.05). The rate increased as a function of duration of use, with the highest rate observed in patients exposed for more than 24 months (1.99, 1.14 to 3.45) and in those with a cumulative dosage greater than 28 000 mg (2.54, 1.05 to 6.14).

Conclusion The use of pioglitazone is associated with an increased risk of incident bladder cancer among people with type 2 diabetes.


  • LA is the recipient of a Chercheur-Boursier award from the Fonds de la recherche en santé du Québec and SS is the recipient of the James McGill Chair.

  • Contributors: All authors participated in the study design. SS acquired the data. LA and HY did the analyses. LA wrote the manuscript and all authors participated in the interpretation of the results and critical revision of the manuscript. LA is the guarantor.

  • Funding: This study was supported by grants from the Canadian Institutes of Health Research and the Canadian Foundation for Innovation. The funding sources had no role in the design, analysis, and interpretation of the results, and thus the authors were independent from the funding source.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: MNP served as a consultant for Novo Nordisk and Sanofi-Aventis and received research funding from Novo Nordisk; no other financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study was approved by the independent scientific advisory committee of the general practice research database and the research ethics committee of the Jewish General Hospital, Montreal, Canada.

  • Data sharing: No additional data available.

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