Thiazolidinedione use and cancer incidence in type 2 diabetes: A systematic review and meta-analysis

Aims. Evidence suggests thiazolidinediones (TZDs) may modify the relationship between type 2 diabetes and cancer incidence. We aimed to summarize data from randomized controlled trials (RCTs) and observational studies to examine risk of overall and site-specific cancers with TZD use in individuals with type 2 diabetes. Methods. - We searched 12 key biomedical databases and seven grey literature sources up to June 2011, without language restrictions. We performed separate meta-analyses according to cancer site and study design, comparing ever-use to never-use of TZDs, and pioglitazone alone. Results. - The search yielded 1338 unique citations; we included four RCT, seven cohort and nine nested case-control studies, contributing data from 2.5 million people. Estimates from observational studies suggested any TZD use was associated with a decreased risk of colorectal (pooled RR: 0.93, 95%CI 0.87-1.00, P = 0.04, I-2 = 30%), lung (pooled RR: 0.91, 95%CI 0.84-0.98, P = 0.02, heterogeneity (I-2) = 35%) and breast (pooled RR: 0.89, 95%CI 0.81-0.98, P = 0.02, I-2 = 44%) cancer. Risk of overall cancer with TZD use was not significantly modified in RCTs (pooled RR: 0.92, 95%CI 0.79-1.07, P = 0.26, I-2 = 0%) or observational studies (pooled OR: 0.95, 95%CI 0.78-1.16, P = 0.63, I-2 = 70%). Pioglitazone use was, however, associated with a decreased risk of overall cancer (colorectal, lung, breast, prostate and renal sub-sites combined) in observational studies (pooled RR: 0.95, 95%CI 0.91-0.99, P = 0.009, I-2 = 0%). Conclusions. - Our findings suggest that use of TZDs is associated with a modest but significantly decreased risk of lung, colorectal and breast cancers. Results were limited by the paucity of studies designed to answer our research question. Further evaluation of TZD use, cancer risk factors and potential confounders is required. (C) 2012 Elsevier Masson SAS. All rights reserved.