Prolonged TZD use might cause bladder cancer.

In several studies, the diabetes drug pioglitazone (Actos) has been associated with risk for bladder cancer (JW Gen Med Jun 21 2012). In this retrospective study, researchers used a U.K. database to compare the incidence of bladder cancer in 18,000 users of thiazolidinedione (TZD) drugs (i.e., pioglitazone and rosiglitazone [Avandia]) and 41,000 users of sulfonylureas. Although median follow-up was about 3 years, follow-up exceeded 5 years in 25% of patients.

Overall, 197 bladder cancers were diagnosed (about 1 case per 300 patients). After adjustment for potential confounders, risk for bladder cancer was significantly higher after 5 years of TZD use (hazard ratio, 3.42 for 5-year users compared with risk in <1-year users). Moreover, 5 years of TZD use was associated with higher incidence of bladder cancer than 5 years of sulfonylurea use (HR, 2.53); with shorter durations of use, incidence was similar in the TZD and sulfonylurea groups. Pioglitazone and rosiglitazone conferred similar risks.

Comment: The evidence for an association between TZDs and bladder cancer — albeit mostly from observational studies — is mounting. The mechanisms are unclear: In basic science studies, agonists of PPAR– (the TZD receptor) affect cell differentiation and proliferation in various ways. In any case, we have little reason to prescribe TZDs, which are not essential for managing diabetes and which are associated with other adverse effects.

Source:Journal Watch General Medicine