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Does Pioglitazone Heighten Risk of Cancer?

Study looks at persons with diabetes

Pioglitazone use for diabetes was not associated with a statistically significant increased risk of bladder cancer in a cohort study of 193,099 individuals aged 40 years and older, although an increased risk could not be excluded from the analysis, including increased prostate and pancreatic cancer risks associated with ever use of the drug. The study also included an analysis of 10 additional cancers in 236,507 individuals aged 40 years and older and concluded:

• 18% of individuals in the bladder cancer cohort received pioglitazone and 1,261 had incident bladder cancer.

• Ever use of pioglitazone was not associated with bladder cancer risk.

• There was no association with 8 of the 10 additional cancers.

• There was increased risk of prostate cancer (HR-1.13) and pancreatic cancer (HR-1.41) from ever use of pioglitazone.

Citation: Lewis JD, Habel LA, Quesenberry CP, et al. Pioglitazone use and risk of bladder cancer and other common cancers in persons with diabetes. JAMA. 2015;314(3):265-277.

Commentary: The reported association between pioglitazone and bladder cancer, was reported first in animal studies, then in the Proactive study in 20051. The concern over this serious potential effect has led to decreased use of pioglitazone over the last decade. This well-done study substantially refutes this concern with data from a large cohort of individuals. The recent American Diabetes Association position paper on management of hyperglycemia supports the conclusion that there is not a documented association between TZDs and bladder cancer2. As for the possible association reported here between pioglitazone and prostate cancer and pancreatic cancer, the increased risk detected was relatively low, and the authors concluded that the risks, “merit further investigation to assess whether the observed associations are causal or due to chance, residual confounding, or reverse causality.” —Neil Skolnik, MD

1. Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the Proactive study (Prospective pioglitazone clinical trial in macrovascular events): a randomized controlled trial. Lancet. 2005;366 (9493):1279-1289.

2. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: A patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015;38:140–149.

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