Cancer Risk for Patients Using Thiazolidinediones for Type 2 Diabetes: A Meta-Analysis

Abstract

Abstract Learning Objectives Evaluate the risk of cancer as well as cardiovascular and renal disease in the use of oral antidiabetics. Define and adequately quantify the effect of TZD on the risk of bladder cancer, other selected cancers, and all neoplasms. Objective. To clarify and quantify the effect of thiazolidinediones (TZDs; e.g., pioglitazone, rosiglitazone) on the risk of bladder cancer, other selected cancers, and overall cancer in patients with type 2 diabetes, we performed a systematic review and meta-analysis of observational studies. Methods. A PubMed/MEDLINE search was conducted for studies published in English up to June 30, 2012. Random-effect models were fitted to estimate summary relative risks (RR). Results. Seventeen studies satisfying inclusion criteria (3 case-control studies and 14 cohort studies) were considered. Use of TZDs was not associated to the risk of cancer overall (summary RR: 0.96; 95% confidence interval [CI]: 0.91–1.01). A modest excess risk of bladder cancer was reported in pioglitazone (RR: 1.20; 95% CI: 1.07–1.34 from six studies) but not in rosiglitazone (RR: 1.08; 95% CI: 0.95–1.23 from three studies) users. The RRs of bladder cancer were higher for longer duration (RR: 1.42 for >2 years) and higher cumulative dose of pioglitazone (RR: 1.64 for >28,000 mg). Inverse relations were observed with colorectal cancer (RR: 0.93; 95% CI: 0.90–0.97 from six cohort studies) and liver cancer (RR: 0.65; 95% CI: 0.48–0.89 from four studies), whereas there was no association with pancreatic, lung, breast, and prostate cancers. Conclusions. Adequate evidence excludes an overall excess cancer risk in TZD users within a few years after starting treatment. However, there is a modest excess risk of bladder cancer, particularly with reference to pioglitazone. Assuming that this association is real, the potential implications on the risk-benefit analysis of TZD use should be evaluated.