FDA, medical societies warn of possible link between pioglitazone, bladder cancer risk

After reviewing data from a 5-year interim analysis of an ongoing, 10-year epidemiological study, the FDA is informing the public of a possible link between prolonged use of pioglitazone and an increased risk for bladder cancer, according to an agency press release.

The warnings and precautions section of the label for pioglitazone-containing medicines will be updated to include information on this risk. Additionally, the patient medication guide for these medicines will also be revised to include this information.

Although there was no overall increased risk for bladder cancer associated with pioglitazone (Actos, Takeda), a 40% increase in disease was observed among patients exposed to pioglitazone for more than 12 months. The risk was also increased among those exposed to the highest cumulative dose.

The planned 5-year interim analysis was performed by Takeda with data collected from Jan. 1, 1997, to April 30, 2008. Among patients treated with pioglitazone, the median duration of therapy was 2 years (range 0.2-8.5 years). After adjusting for age, sex, use of tobacco products, use of other categories of diabetes medications and other risk factors, there was no significant increase in the risk for bladder cancer in patients exposed to pioglitazone compared with those never exposed (HR=1.2, 95% CI, 0.9-1.5).

However, the risk for bladder cancer increased as the dose and duration of pioglitazone increased. Being treated with pioglitazone for more than 12 months was associated with a 40% increase in the risk for bladder cancer vs. never being treated with pioglitazone (HR=1.4; 95% CI, 0.9-2.1). After more than 24 months of pioglitazone use, the HR was 1.4 (95% CI, 1.03-2.0) and was of nominal statistical significance. Based on these data, the FDA calculated that duration of therapy for more than 12 months was associated with 27.5 excess cases of bladder cancer per 100,000 person-years follow-up vs. never use of pioglitazone, according to the press release.

Recently, France suspended the use of pioglitazone due to results of an epidemiological study suggesting an increased risk for bladder cancer with pioglitazone. Germany has also recommended against starting pioglitazone in new patients.

The FDA has made the following recommendations to health care providers:

Do not use pioglitazone in patients with active bladder cancer.
Use pioglitazone with caution in patients with a prior history of bladder cancer. The benefits of blood sugar control with pioglitazone should be weighed against the unknown risks for cancer recurrence.

In addition, The Endocrine Society, the American Association of Clinical Endocrinologists and the American Diabetes Association is are now urging patients currently taking pioglitazone or any combination of medication that includes pioglitazone, to continue taking all currently prescribed medications unless otherwise instructed by their health care provider.

The FDA will continue to evaluate data from the ongoing, 10-year epidemiological study and will also conduct a comprehensive review of the results from the French study. Once more information is available, the FDA will update the public.

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