Pioglitazone and risk of bladder cancer in type 2 diabetes mellitus patients: A systematic literature review and meta-analysis of observational studies using real-world data

Abstract

ObjectivesPatients with type 2 diabetes mellitus (T2DM) have a higher incidence of bladder cancer (BC); however, the evidence underlining the association between pioglitazone use and BC risk remains inconclusive. We conducted a systematic review and meta-analysis of observational studies to investigate the effect of pioglitazone on risk of BC in T2DM patients. MethodsWe searched all publications regarding risk of BC with pioglitazone use through PubMed, Web of Science and Cochrane library databases from inception to March, 2017. Pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. ResultsTotal 15 observational (9 cohort and 6 case-control) studies were meta-analyzed. The pooled results showed a significant association between risk of BC and pioglitazone use (HR 1.20, 95%CI 1.09–1.31; P<0.0001; I2=4%). In subgroup analysis, cumulative dose of pioglitazone (− and >mg) showed a significant association with risk of BC (HR 1.27; 95%CI 1.05–1.54; P=0.01; I2=0% and HR 1.68, 95%CI 1.36–2.08; P<0 I2=0% respectively). In addition, a significant association was seen with risk of BC and pioglitazone treatment duration (12–24 months and >24 months) (HR 1.43; 95%CI 1.19–1.71; P=0.0001; I2=0% and HR 1.58; 95%CI 1.27–1.97; P<0.0001; I2=29% respectively). Meta-analysis of pioglitazone vs. rosiglitazone use, showed a significant association (HR 1.34; 95%CI 1.05–1.71; P=0.02; I2=0%) with BC risk and pioglitazone use. ConclusionPioglitazone use is associated with risk of BC in T2DM patients. Risk of bladder cancer appears to be associated with higher dose and longer duration of pioglitazone use.