Use of thiazolidinediones and the risk of bladder cancer among people with type 2 diabetes: a meta-analysis

Abstract

Background: Patients with type 2 diabetes have a 40% increased risk of bladder cancer. Thiazolidinediones, especially pioglitazone, may increase the risk. We conducted a systematic review and meta-analysis to evaluate the risk of bladder cancer among adults with type 2 diabetes taking thiazolidinediones.

Methods: We searched key biomedical databases (including MEDLINE, Embase and Scopus) and sources of grey literature from inception through March 2012 for published and unpublished studies, without language restrictions. We included randomized controlled trials (RCTs), cohort studies and case-control studies that reported incident bladder cancer among people with type 2 diabetes who ever (v. never) were exposed to pioglitazone (main outcome), rosiglitazone or any thiazolidinedione.

Results: Of the 1787 studies identified, we selected 4 RCTs, 5 cohort studies and 1 case-control study. The total number of patients was 2,657,365, of whom 3643 had newly diagnosed bladder cancer, for an overall incidence of 53.1 per 100,000 person-years. The one RCT that reported on pioglitazone use found no significant association with bladder cancer (risk ratio [RR] 2.36, 95% confidence interval [CI] 0.91-6.13). The cohort studies of thiazolidinediones (pooled RR 1.15, 95% CI 1.04-1.26; I(2) = 0%) and of pioglitazone specifically (pooled RR 1.22, 95% CI 1.07-1.39; I(2) = 0%) showed significant associations with bladder cancer. No significant association with bladder cancer was observed in the two RCTs that evaluated rosiglitazone use (pooled RR 0.87, 95% CI 0.34-2.23; I(2) = 0%).

Interpretation: The limited evidence available supports the hypothesis that thiazolidinediones, particularly pioglitazone, are associated with an increased risk of bladder cancer among adults with type 2 diabetes.

Figure 1:

Selection of studies.

Figure 2:

Meta-analysis of the risk of bladder cancer associated with pioglitazone use among adults with type 2 diabetes in cohort studies. A value greater than 1.0 indicates an increased risk of bladder cancer with pioglitazone use. CI = confidence interval.

Figure 3:

Meta-analysis of the risk of bladder cancer associated with rosiglitazone use among patients with type 2 diabetes in randomized controlled trials. A value greater than 1.0 indicates an increased risk of bladder cancer with rosiglitazone use. CI = confidence interval.

Figure 4:

Meta-analysis of the risk of bladder cancer associated with the use of any thiazolidinedione in randomized controlled trials (A) and cohort studies (B). A value greater than 1.0 indicates an increased risk of bladder cancer with the use of any thiazolidinedione. *A total of 178 cases of bladder cancer occurred in the study population. †Pioglitazone; ‡rosiglitazone. CI = confidence interval, NR = not reported.