Pioglitazone use in patients with diabetes and risk of bladder cancer: a systematic review and meta-analysis

Pioglitazone has been reported to increase the risk of bladder cancer but the conclusions of published clinical studies are confusing. We conducted a systematic review and meta-analysis of all eligible randomized controlled trial (RCT) studies and observational studies, in order to identify a more precise relationship between pioglitazone and risk of bladder cancer. We searched for publications up to January 24, 2018, in PubMed, EMBASE, Scopus, Web of Science, Cochrane register, and Chinese National Knowledge Infrastructure databases, and the references of the retrieved articles and relevant reviews were also checked. Relative risk and 95% confidence interval (CI) were used to assess this correlation. A dose-related meta-analysis was performed as well. Data on RCT studies showed a null association between pioglitazone and bladder cancer. The pooled RR estimates of the 12 included studies illustrated that pioglitazone is associated with a 14% increased risk of bladder cancer (95% CI 1.03-1.26). No evidence of publication bias was detected. In the dose effect analysis, patients who used a higher dose of pioglitazone had an increased risk of bladder cancer. In conclusion, this meta-analysis indicated that pioglitazone is associated with an increased risk of bladder cancer. Further research should be conducted to confirm our findings and reveal the potential biological mechanisms.