Pioglitazone and bladder cancer

Pioglitazone is contraindicated in patients with bladder cancer or a history of bladder cancer, or in patients with uninvestigated macroscopic haematuria. Risk factors for bladder cancer (age, smoking history, exposure to some occupational or chemotherapy agents or prior radiation treatment in the pelvic region) should be assessed before initiating pioglitazone, and any macroscopic or microscopic haematuria investigated (1).

A systematic review and meta-analysis concerning the risk of bladder cancer with thiazolidinediones has been undertaken (2).

• the analysis screened 230 citations and included 18 studies, comprising five randomized controlled trials (RCTs) and 13 observational studies
  • meta-analysis showed a significantly higher overall risk of bladder cancer with pioglitazone in RCTs [7878 participants; odds ratio (OR) 2.51, 95% confidence interval (CI) 1.09-5.80] and observational studies (>2.6 million patients; OR for 'ever' users vs. non-users 1.21, 95% CI 1.09-1.35)
    • subgroup analysis of observational studies by cumulative dose showed the risk of bladder cancer to be greatest with >28.0g of pioglitazone (OR 1.64, 95% CI 1.28-2.12)
      
      
    • a significantly increased risk was found with both 12-24 months (OR 1.41, 95% CI 1.16-1.71) and >24 months (OR 1.51, 95% CI 1.26-1.81) cumulative durations of pioglitazone exposure
      
      
    • no significant risk was seen with rosiglitazone in RCTs (OR 0.84, 95% CI 0.35-2.04) or 'ever' users vs. non-users in observational studies (OR 1.03, 95% CI 0.94-1.12); the evidence for any relationship between bladder cancer risk and rosiglitazone cumulative duration is limited and inconsistent
      
      
• the study authors concluded that there was "..A modest but clinically significant increase in the risk of bladder cancer with pioglitazone was found, which appears to be related to cumulative dose and duration of exposure. We recommend that prescribers limit pioglitazone use to shorter durations..." (2)

Reference:

1. MeReC Bulletin (2012);22;5
2. Turner RM et al. Thiazolidinediones and associated risk of bladder cancer: a systematic review and meta-analysis. Br J Clin Pharmacol. 2014 Aug;78(2):258-73.