Pioglitazone and risk of bladder cancer: a meta-analysis of controlled studies

Diabet Med. 2013 Sep;30(9):1026-32. doi: 10.1111/dme.12144.


Aims: Pioglitazone, a thiazolidinedione, was approved for treatment of Type 2 diabetes. However, several observational studies suggest an association of pioglitazone with an increased risk of bladder cancer in patients with diabetes. Therefore, we sought to perform a systematic review and meta-analysis to evaluate the magnitude of this association and the quality of the supporting evidence.

Methods: Electronic databases were queried to identify controlled studies of pioglitazone that measured the risk of bladder cancer.

Results: Six studies involving 215 142 patients using pioglitazone were included, with a median period of follow-up of 44 months. The hazard of developing bladder cancer was significantly higher in patients using pioglitazone (hazard ratio 1.23; 95% CI 1.09-1.39; I² = 0%) compared with control groups. The risk of bias was moderate across the six studies. Considering an incidence rate of 20.8 per 100 000 person years, the number needed to harm was five additional cases of bladder cancer per 100 000 person years.

Conclusions: Patients treated with pioglitazone have a slight increased risk of bladder cancer compared to general population. Patient involvement and weighing treatment benefits versus risks should be discussed with patient toward shared decision. Patients with type 2 diabetes with risk factors, such as family history, smoking, or exposure to certain forms of chemotherapy may need to consider other anti-hyperglycemic agents. Also, pioglitazone should be discontinued in type 2 diabetes patients with newly diagnosed bladder cancer.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Controlled Clinical Trials as Topic
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Follow-Up Studies
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use
  • Pioglitazone
  • Risk
  • Thiazolidinediones / adverse effects*
  • Thiazolidinediones / therapeutic use
  • Urinary Bladder Neoplasms / chemically induced*
  • Urinary Bladder Neoplasms / complications
  • Urinary Bladder Neoplasms / epidemiology


  • Hypoglycemic Agents
  • Thiazolidinediones
  • Pioglitazone