Risk of Bladder Cancer Among Diabetic Patients Treated With Pioglitazone

Interim report of a longitudinal cohort study

  1. Brian L. Strom, MD, MPH1,2,5
  1. 1Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania
  2. 2Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania
  3. 3Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
  4. 4Division of Research, Kaiser Permanente Northern California, Oakland, California
  5. 5Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania
  1. Corresponding author: James D. Lewis, lewisjd{at}


OBJECTIVE Some preclinical in vivo studies and limited human data suggest a possible increased risk of bladder cancer with pioglitazone therapy. This is an interim report of an ongoing cohort study examining the association between pioglitazone therapy and the risk of bladder cancer in patients with diabetes.

RESEARCH DESIGN AND METHODS This study includes 193,099 patients in the Kaiser Permanente Northern California diabetes registry who were ≥40 years of age between 1997 and 2002. Those with prior bladder cancer were excluded. Ever use of each diabetes medication (defined as two or more prescriptions within 6 months) was treated as a time-dependent variable. Cox regression–generated hazard ratios (HRs) compared pioglitazone use with nonpioglitazone use adjusted for age, sex, race/ethnicity, diabetes medications, A1C, heart failure, household income, renal function, other bladder conditions, and smoking.

RESULTS The group treated with pioglitazone comprised 30,173 patients. There were 90 cases of bladder cancer among pioglitazone users and 791 cases of bladder cancer among nonpioglitazone users. Overall, ever use of pioglitazone was not associated with risk of bladder cancer (HR 1.2 [95% CI 0.9–1.5]), with similar results in men and women (test for interaction P = 0.8). However, in the a priori category of >24 months of therapy, there was an increased risk (1.4 [1.03–2.0]). Ninety-five percent of cancers diagnosed among pioglitazone users were detected at early stage.

CONCLUSIONS In this cohort of patients with diabetes, short-term use of pioglitazone was not associated with an increased incidence of bladder cancer, but use for more than 2 years was weakly associated with increased risk.

  • Received June 4, 2010.
  • Accepted January 18, 2011.

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