Pioglitazone associated with increased rates of bladder cancer
Pioglitazone was associated with an increased risk of bladder cancer, but rosiglitazone was not, in a large recent meta-analysis.
Pioglitazone was associated with an increased risk of bladder cancer, but rosiglitazone was not, in a large recent meta-analysis.
Researchers looked for published and unpublished randomized, controlled trials, cohort studies and case-control studies that reported incident bladder cancer among people with type 2 diabetes who used pioglitazone, rosiglitazone or any thiazolinedione through March 2012.
Results appeared online July 3 in CMAJ. Researchers found four randomized, controlled trials, five cohort studies and one case-control study, with a total of more than two million patients and 3,643 newly diagnosed cases of bladder cancer, an overall incidence of 53.1 per 100,000 person-years.
All of the five studies assessing pioglitazone reported an elevated or significantly increased risk of bladder cancer associated with any pioglitazone use, compared to those who had never used the drug. A significant association with bladder cancer was reported in one study after more than 12 months' exposure and in two studies that assessed exposure after more than 24 months, the researchers noted.
Two studies reported results of a cumulative pioglitazone dose of more than 28,000 mg. One reported a significant association (hazard ratio [HR], 1.75; 95% CI; 1.22 to 2.50) and the other reported a nonsignificant association (HR, 1.4; 95% CI, 0.96 to 2.1). A third study looked at a dose of 10,500 mg of pioglitazone and found no association.
One randomized, controlled trial found that 14 of 2,605 pioglitazone users and six of 2,633 controls had newly diagnosed bladder cancer (risk ratio [RR], 2.36; 95% CI, 0.91 to 6.13). A case/noncase study reported significantly increased odds of pioglitazone use among patients who developed bladder cancer (odds ratio, 4.30; 95% CI, 2.82 to 6.52). When the results from the three cohort studies of pioglitazone were pooled, there was a significantly increased risk of bladder cancer associated with pioglitazone (pooled RR, 1.22; 95% CI, 1.07 to 1.39; I2=0%).
No significant association with bladder cancer was observed in the two randomized, controlled trials that evaluated rosiglitazone use (pooled RR, 0.87; 95% CI, 0.34 to 2.23; I2=0%). For the thiazolidinedione drug class as a whole, four randomized, controlled trials of more than 14,000 patients found an elevated but not statistically significant association (RR, 1.45; 95% CI, 0.75 to 2.83; I2=2%).
The authors concluded, “Although the absolute risk of bladder cancer associated with pioglitazone was small, other evidence-based treatments for type 2 diabetes may be equally effective and do not carry a risk of cancer.”