Risk of Bladder Cancer Among Diabetic Patients Treated With Pioglitazone

Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia,Pennsylvania, USA.
Diabetes care (Impact Factor: 8.42). 04/2011; 34(4):916-22. DOI: 10.2337/dc10-1068
Source: PubMed


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.
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.
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.
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.

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    • "Overall, every use of pioglitazone was not associated with risk of bladder cancer (HR 1.2, 95% CI 0.9–1.5) [89]. Similar results, though, were obtained from a population-based cohort study (data from the French National Health Insurance Information System, the cohort included 1,491,060 diabetic patients, 155,535 of whom were exposed to pioglitazone); increased incidence of bladder cancer was associated with high cumulative doses (≥28,000 mg, HR 1.75, 95% CI 1.22–2.50, "
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    • "In June 2011, a French study suggested an increased risk of bladder cancer in patients who were treated with pioglitazone for more than one year leading to a temporary withdrawal of pioglitazone by the French Agency [18]. Another study in the US also indicated a possible increase in bladder cancer risk in patients on pioglitazone for more than 2 years, compared with diabetes patients who were not receiving pioglitazone [19,20]. The TGA, as well as FDA and EMA, announced safety warnings outlining a possible risk of bladder cancer related to pioglitazone use in June-July 2011; however, there have been no further updates on this issue [21-23]. "
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