Spotlight on pioglitazone

Evidence on possible risks of pioglitazone made the news in the past month.

First, the FDA released the results an updated review of the association between pioglitazone and bladder cancer. Although results of the reviewed studies varied, overall the data suggest that pioglitazone use may be linked to an increased risk of bladder cancer, the agency concluded. Drugs that contain pioglitazone have carried labels warning about this risk since 2011, but they will now be updated to describe the additional research. The FDA recommends against using pioglitazone in patients with active bladder cancer and urges clinicians to carefully consider risks and benefits before using it in patients with a history of bladder cancer, according to a safety announcement issued on Dec. 12.

Pioglitazone appears not to be associated with prostate cancer, according to a manufacturer-funded, nested case-control study published by BMJ Open Diabetes Research & Care on Dec. 9. From a cohort of almost 50,000 English men, researchers identified 756 patients with prostate cancer, whom they compared with 2,942 controls. Forty-two of the cases had taken pioglitazone, as had 202 of the controls. The study found no association between prostate cancer risk and pioglitazone use, overall or in subgroup analyses. The authors noted that this finding differs from some previous studies but that the finding of an association in other research could have been due to chance or confounding. The current study “provides reassurance to clinicians and policymakers as to the safety of pioglitazone,” the authors said.

However, another recent study, published in the Journal of Clinical Endocrinology & Metabolism on Dec. 9, found that pioglitazone may be associated with fracture risk in some patients. The Insulin Resistance Intervention after Stroke trial included 3,876 patients who had an ischemic stroke or transient ischemic attack and insulin resistance but not diabetes and were randomized to pioglitazone or placebo. The original trial found that pioglitazone reduced risk of stroke and myocardial infarction, but this analysis found fractures to be more common in patients on pioglitazone (13.6% vs. 8.8%; hazard ratio, 1.53 [95% CI, 1.24 to 1.89]). The pioglitazone group also had a higher rate of serious fractures most likely to be related to pioglitazone (those not related to trauma or malignancy). The study data can be used to help patients make an individual decision about the risks versus benefits of pioglitazone therapy, the authors noted.