The diabetes drug pioglitazone (Actos, Takeda Pharmaceuticals) is associated with an increased risk of bladder cancer, according to a study published in the British Medical Journal. The findings suggest that the risk increases with increasing duration of use and dose. No increased risk was seen for a similar drug, rosiglitazone (Avandia, GlaxoSmithKline).
Pioglitazone and rosiglitazone belong to a class of drugs called thiazolidinediones, which help to control blood sugar in patients with type-2 diabetes. However, in 2005, a trial unexpectedly showed an imbalance in the number of bladder cancer cases with pioglitazone compared with placebo. Since then, the association between the use of pioglitazone and bladder cancer has been controversial, with studies reporting contradictory findings.
A team of Canadian-based researchers therefore set out to determine whether the use of pioglitazone, when compared with other antidiabetic drugs, was associated with an increased risk of bladder cancer in patients with type-2 diabetes. They analyzed data from 145,806 patients in the United Kingdom’s Clinical Practice Research Database (CPRD) who were newly treated with diabetes drugs between January 2000 and July 2013. Potential influential factors, such as age, sex, duration of diabetes, smoking status, and alcohol-related disorders, were taken into account.
The cohort generated 689,616 person-years of follow-up, during which 622 patients were newly diagnosed as having bladder cancer (crude incidence, 90.2 per 100,000 person-years). Compared with other antidiabetic drugs, pioglitazone was associated with a 63% increased risk of bladder cancer (121.0 vs. 88.9 per 100,000 person-years; hazard ratio [HR], 1.63). Conversely, rosiglitazone was not associated with an increased risk of bladder cancer (86.2 vs. 88.9 per 100,000 person years; HR, 1.10), suggesting that the risk is drug-specific and not a class effect. The results remained largely unchanged after further sensitivity analyses.
The authors stress that, in absolute terms, the risk of bladder cancer remains low. But they suggest that doctors and patients should be aware of this association when assessing the overall risks and benefits of pioglitazone.
In an accompanying editorial, Dr. Victor Montori, a professor of medicine at the Mayo Clinic, suggests that, when working closely with their clinicians, “patients can identify the agent that is best for them given their context, both clinical and personal.”
He points out that observational evidence can help, but warns that “sometimes even large practice databases are too small and incomplete to provide reliable estimates.” He calls for broad collaboration and shared decision making “to compensate for imperfect and sometimes corrupt information, with a humble and generous commitment to understand fully what is best for each patient.”