Increased risk of bladder cancer with pioglitazone therapy in patients with diabetes: a meta-analysis.
OBJECTIVE
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.
Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Zhaowei
Z
Zhu
Zhoujun
Z
Shen
Yingli
Y
Lu
Shan
S
Zhong
Chen
C
Xu
D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D000077205:Pioglitazone; D012307:Risk Factors; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000453:epidemiology
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone