The thiazolidinedione pioglitazone, which targets insulin resistance in type 2 diabetes, demonstrated no connection with bladder cancer in an extensive analysis.


Some animal and human studies have implicated pioglitazone in increasing the risk of bladder cancer. In the new report, appearing online ahead of print in Diabetologia, Daniel Levin, MD, and colleagues studied data from 1.01 million persons in 6 populations around the world, covering 5.9 million person-years, to investigate a dose-response relationship between pioglitazone and risk for bladder cancer. 


The researchers worked with prescription, cancer, and mortality data for persons with type 2 diabetes from British Columbia, Canada; Finland; Manchester, United Kingdom; Rotterdam, Netherlands; Scotland; and the U.K. Clinical Practice Research Datalink, which included 566 general practices in the United Kingdom. The authors noted in their paper that Europe and North America have the highest incidence of bladder cancer, with a higher incidence in patients with diabetes.


Of the 3,248 cases of incident bladder cancer uncovered during median follow-up duration of 4.0 to 7.4 years, only 117 cases occurred in patients who were ever exposed to pioglitazone. Similarly, no association was found between bladder cancer and another thiazolidinedione, rosiglitazone. 



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“Our large international analysis does not support a causal effect of pioglitazone on bladder cancer, thus contradicting previous studies deemed to have proven this relationship,” concluded Levin and fellow investigators. “To fully resolve this controversy, future analyses are needed, involving longer follow-up of exposed persons and using methods to minimize allocation bias.” n