An updated meta-analysis of pioglitazone exposure and bladder cancer and comparison to the drug's effect on cardiovascular disease and non-alcoholic steatohepatitis

Diabetes Res Clin Pract. 2018 Jan:135:102-110. doi: 10.1016/j.diabres.2017.11.002. Epub 2017 Nov 13.

Abstract

Aim: We performed a meta-analysis of epidemiological studies evaluating exposure to pioglitazone and the risk for bladder cancer and compared these results to the drug's effects on cardiovascular disease (CVD) and non-alcoholic steatohepatitis (NASH).

Methods: Pubmed and Embase were searched for cohort and case control studies for all years through 2016.

Results: Data from 17 papers were analyzed. In cohort studies, 822 of 357,888 pioglitazone-exposed patients (0.23%) developed bladder cancer while 7691 of 2,898,682 unexposed (0.26%) did. In case control studies, 3219 of 1,146,916 patients (0.28%) developed bladder cancer. A random effects model showed no significant association between ever vs never use or with cumulative doses of pioglitazone. However, there was a significant association with 1-2 years (HR = 1.28 [1.08-1.55]) and >2 years (HR = 1.42 [1.14-1.77]) of exposure. The numbers needed to treat for one additional case of bladder cancer ranged from 899 to 6380 while to benefit CVD and NASH, 4-256 and 2-12, respectively.

Conclusions: Given the very small prevalence of bladder cancer in diabetic patients exposed (or not) to pioglitazone (<0.3%) and the much greater beneficial effects of the drug on CVD and NASH, the use of pioglitazone should be resurrected.

Keywords: Bladder cancer; Cardiovascular disease; Non-alcoholic steatohepatitis; Pioglitazone.

Publication types

  • Meta-Analysis

MeSH terms

  • Cardiovascular Diseases / etiology*
  • Cohort Studies
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / pharmacology
  • Non-alcoholic Fatty Liver Disease / etiology*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Pioglitazone
  • Prevalence
  • Risk
  • Thiazolidinediones / adverse effects*
  • Thiazolidinediones / pharmacology
  • Urinary Bladder Neoplasms / epidemiology
  • Urinary Bladder Neoplasms / etiology*
  • Urinary Bladder Neoplasms / pathology

Substances

  • Hypoglycemic Agents
  • Thiazolidinediones
  • Pioglitazone