FDA Warns of Bladder Cancer Risk From Diabetes Drug

The US Food and Drug Administration (FDA) has concluded that pioglitazone, used to treat type 2 diabetes, may be linked to an increased risk of bladder cancer. The studies on this topic have yielded mixed results, but the FDA urges caution when prescribing this agent.

Pioglitazone was approved to improve blood sugar control in adult patients with type 2 diabetes. In August 2011, the FDA approved additional labeling for the drug, which instructed physicians not to use pioglitazone in patients with active bladder cancer, and to “use pioglitazone with caution in patients with a prior history of bladder cancer.”

The new update includes further studies and results reviewed in the interim. One such study was a 10-year prospective cohort study conducted by the drug’s manufacturer (Takeda Pharmaceuticals); it included a total of 158,918 individuals who never took pioglitazone, and 34,181 patients who had taken the agent at some point. The “never users” were followed for an average of 8.9 years, and the “ever users” were followed for 6.1 years.

There were a total of 1,075 cases of bladder cancer in the never users, and 186 cases in the ever users. This yielded a hazard ratio of 1.06 (95% CI, 0.89–1.26).

The FDA noted that there was a trend toward higher risk with increasing duration of pioglitazone, but this did not reach significance. A retrospective cohort study, however, did find a significant association. This study included 145,806 patients newly treated with antidiabetic drugs, including 10,951 “initiators” of pioglitazone. Over a mean follow-up of 4.7 years, there were 622 new cases of bladder cancer, and 54 of those were developed following pioglitazone exposure. The adjusted HR for bladder cancer after pioglitazone use compared with no use of any thiazolidinedione was 1.63 (95% CI, 1.22–2.19). Again, longer use and larger cumulative dose raised the risk, this time significantly.

The FDA still says the drug should not be used in those with active bladder cancer and that caution in prescribing in others is warranted. The new labeling will include updated results of available studies on this topic.