Increased risk of bladder cancer with pioglitazone therapy in patients with diabetes: a meta-analysis.

AIMS: Emerging studies suggest a possible increased risk of bladder cancer with pioglitazone therapy. We therefore pooled data available to examine the association between pioglitazone therapy and bladder cancer in patients with diabetes.

METHODS: We searched Medline and Embase to identify studies that reported the effect of pioglitazone on bladder cancer among diabetic patients. Summary effect estimates were derived using a fixed-effects meta-analysis model.

RESULTS: Five studies included 2,350,908 diabetic patients. Pioglitazone was associated with a significantly higher risk of bladder cancer (relative risk [RR] 1.17, 95% confidence interval (CI) 1.03-1.32, P=0.013). No relation between pioglitazone and bladder cancer was found for duration of therapy <12 months and cumulative dose <28,000 mg. The RR for bladder cancer in subjects with 12-24 months of pioglitazone use was 1.34 (95% CI 1.08-1.66, P=0.008). The effect was even stronger for cumulative treatment duration >24 months (RR 1.38, 95% CI 1.12-1.70, P=0.003). There was a significant risk for patients with cumulative dose >28,000 mg (RR 1.58, 95% CI 1.12-2.06, P=0.001).

CONCLUSIONS: Pioglitazone treatment appears to be associated with a significantly increased risk of bladder cancer in patients with diabetes.