Association Between Longer Therapy With Thiazolidinediones and Risk of Bladder Cancer: A Cohort Study
Journal of the National Cancer Institute, 08/10/2012
Mamtani R et al. – Long–term thiazolidinedione (TZD) therapy (≥5years) in patients with type 2 diabetes may be associated with an increased risk of bladder cancer, which may be common to all TZDs.Methods
- The authors conducted a retrospective cohort study of patients with type 2 diabetes mellitus who initiated treatment with a TZD (n=18459 patients) or a sulfonylurea (SU) (n=41396 patients) between July 1,2000, and August 31,2010, using The Health Improvement Network database in the United Kingdom.
- Incident cancers were identified for 196 708 person-years of follow-up.
- Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of bladder cancer in the TZD cohort compared with the SU cohort (referent), adjusted for potential confounders.
- Risk associated with increasing duration of drug exposure was also examined.
- All statistical tests were two-sided.
- The authors identified 60 incident bladder cancers in the TZD cohort and 137 cancers in the SU cohort.
- No difference in bladder cancer risk was found between the two cohorts (TZD vs SU, HR=0.93, 95% CI=0.68 to 1.29) in analyses that did not account for duration of exposure.
- However, the risk of bladder cancer was increased among patients with the longest duration of TZD vs SU therapy (≥5years of use, HR=3.25, 95% CI=1.08 to 9.71) and among those with the longest time since initiation of therapy (≥5years since first use, HR=2.53, 95% CI=1.12 to 5.77).
- Risk of bladder cancer also increased with increasing time since initiation of pioglitazone (P trend<.001) and rosiglitazone (P trend=.006).
- Comparison of pioglitazone to rosiglitazone use did not demonstrate difference in cancer risk (P=.49).