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

Diabetes Res Clin Pract. 2012 Oct;98(1):159-63. doi: 10.1016/j.diabres.2012.05.006. Epub 2012 Jun 16.


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.

Publication types

  • Meta-Analysis

MeSH terms

  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Male
  • Pioglitazone
  • Risk Factors
  • Thiazolidinediones / administration & dosage
  • Thiazolidinediones / adverse effects*
  • Urinary Bladder Neoplasms / chemically induced*
  • Urinary Bladder Neoplasms / epidemiology


  • Hypoglycemic Agents
  • Thiazolidinediones
  • Pioglitazone