Pioglitazone is Associated With Excess Risk for Bladder Cancer

Paul S. Mueller, MD, MPH, FACP

Journal Watch 

Abstract and Introduction


Using pioglitazone for >2 years or exceeding a cumulative dose of 28,000 mg imparted the highest risk.


In 2011, the FDA issued a safety warning for the antidiabetic drug pioglitazone (Actos). The warning states that use for longer than 1 year might be associated with excess risk for bladder cancer, based on data from a French study and an interim analysis of a manufacturer-sponsored, U.S. observational study. U.K. investigators now report on a case-control study in which they evaluated the same outcome.

Researchers identified 116,000 patients (mean age, 64) with type 2 diabetes who were new users of oral antidiabetic drugs. After a mean follow-up of 4.6 years, 470 patients had received diagnoses of bladder cancer (89 cases per 100,000 person-years). Each patient with bladder cancer was matched with as many as 20 controls. Ever use of pioglitazone was associated with 83% higher risk for bladder cancer — a significant increase — compared with never users. The bladder cancer rate increased significantly with duration of pioglitazone use, with the highest rates in patients who were exposed for >2 years, and in patients whose cumulative dose exceeded 28,000 mg. Notably, no excess risk for bladder cancer was observed for patients who received rosiglitazone (Avandia).


In this study, pioglitazone use was associated with excess risk for bladder cancer in patients with type 2 diabetes. Because these findings reinforce the FDA warning, clinicians and patients should weigh carefully the benefits and risks of using this drug.


  1. Azoulay L et al. The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: Nested case-control study. BMJ 2012 May 31; 344:e3645. (https://dx.doi.org/10.1136/bmj.e3645)