Pioglitazone Shows No Significant Association With Bladder Cancer Risk

The use of the diabetes drug pioglitazone was not associated with a significantly increased risk of bladder cancer, as has previously been reported, in a large cohort study. However, the drug was associated with increased risk of both prostate and pancreatic cancers.

Thiazolidinediones, which include pioglitazone, rosiglitazone, and troglitazone, have been used to treat as many as 26% of diabetes mellitus patients. There have been controversies, however, surrounding their safety, including issues of hepatotoxicity and cardiotoxicity. “Pioglitazone is the only thiazolidinedione commonly used worldwide today,” wrote study authors led by James D. Lewis, MD, of the University of Pennsylvania in Philadelphia.

Among the safety concerns with pioglitazone is a possible association with bladder cancer. The new study used cohort and nested case-control analyses of a cohort including 193,099 patients; an additional analysis of 10 other cancers included 236,507 patients. Both cohorts were from Kaiser Permanente Northern California; results were published in JAMA.

Among the bladder cancer cohort, 34,181 patients (18%) received pioglitazone for a median of 2.8 years, and 1,261 had incident bladder cancer. The pioglitazone users had a crude bladder cancer incidence of 89.8 per 100,000 person-years, compared to 75.9 per 100,000 person-years in non-users.

In spite of that difference, ever use of pioglitazone was not associated with an increased risk of bladder cancer, with an adjusted hazard ratio (HR) of 1.06 (95% confidence interval [CI], 0.89–1.26).

The case-control analysis, which included 464 bladder cancer patients and 464 matched control patients, showed similar results. Among bladder cancer patients, 19.6% used pioglitazone, compared with 17.5% among controls, for an adjusted odds ratio of 1.18 (95% CI, 0.78–1.80).

A further analysis showed that there was no association with pioglitazone use of any particular duration. This differed from an interim analysis, which showed an increased risk with 2 years or more of pioglitazone use. The authors wrote that this difference from the earlier analysis remains an important question.

Ever use of pioglitazone was associated with an increased risk of 2 of the other 10 cancers studied. This included prostate cancer, with an HR of 1.13 (95% CI, 1.02–1.26), and pancreatic cancer, with an HR of 1.41 (95% CI, 1.16–1.71).

The authors wrote that “a small increased risk, as previously observed, could not be excluded” with regards to bladder cancer. “The increased prostate and pancreatic cancer risks associated with ever use of pioglitazone merit further investigation to assess whether the observed associations are causal or due to chance, residual confounding, or reverse causality,” they concluded.