The impact of thiazolidinediones on the risk for prostate cancer in patients with type 2 diabetes mellitus: A review and meta-analysis

Thiazolidinediones (TZDs) are a class of anti-diabetic drugs reported to exert anticancer effects in thyroid and lung cancer, but the use of the TZD, pioglitazone, is strongly associated with an increased risk for bladder cancer. This study quantitatively analyzed evidence from observational studies and randomized controlled trials (RCTs) in order to assess the risk for prostate cancer in subjects with type 2 diabetes mellitus (T2DM) using thiazolidinediones (TZDs), versus TZD non-users or users of other anti-diabetic drugs. Studies included based on the PICOSL (Population, Intervention, Comparison, Outcome, Study-design, Language) principle, and were assessed for quality by the Newcastle-Ottawa Scale (NOS) and Cochrane Collaboration's tool. Finally, 9 studies were included in the meta-analysis: 3 case-control studies comprising 1145 TZD-users and 13,392 TZD non-users; 3 cohort studies comprising 41,811 TZD-users and 321,244 TZD non-users; and, 3 RCTs comprising 4246 TZD-users and 12,465 TZD non-users. Data analysis revealed that TZD use confers a low [pooled Odds Ratio (OR) = 0.88 at 95% CI (confidence interval) (0.75–1.02) from case-control studies] to marginal [pooled Risk Ratio (RR) =0.94 at 95% CI (0.80–1.10) from cohort studies and pooled RR = 0.97 at 95% CI (0.78–1.20) from RCTs] protective effect on T2DM patients, with regard to prostate cancer incidence. Thus, it may be concluded that TZDs does not increase the risk for prostate cancer in patients of T2DM, when compared to TZD non-users or users of metformin, insulin secretagogues, insulin and sulfonylurea. However, more clinical trials are required to validate the clinical significance of these findings.