Medical oncology, Cancérologie, Sciences biologiques et medicales, Biological and medical sciences, Sciences medicales, Medical sciences, Tumeurs, Tumors, Nephrologie. Maladies des voies urinaires, Nephrology. Urinary tract diseases, Tumeurs de l'appareil urinaire, Tumors of the urinary system, Voies urinaires. Prostate, Urinary tract. Prostate gland, Agoniste, Agonist, Agonista, Cancer, Cáncer, Dérivé de la thiazolidinedione, Thiazolidinedione derivatives, Tiazolidinediona derivado, Endocrinopathie, Endocrinopathy, Endocrinopatía, Maladie métabolique, Metabolic diseases, Metabolismo patología, Pathologie de l'appareil urinaire, Urinary system disease, Aparato urinario patología, Pathologie de la vessie, Bladder disease, Vejiga patología, Pathologie des voies urinaires, Urinary tract disease, Vía urinaria patología, Récepteur PPAR-γ, PPAR-γ receptor, Receptor PPAR-γ, Santé publique, Public health, Salud pública, Tumeur maligne, Malignant tumor, Tumor maligno, Cancer de la vessie, Bladder cancer, Cáncer de la vejiga, Cancérologie, Cancerology, Cancerología, Diabète de type 2, Type 2 diabetes, Diabetes de tipo 2, Epidémiologie, Epidemiology, Epidemiología, Etude cohorte, Cohort study, Estudio cohorte, Facteur risque, Risk factor, Factor riesgo, Homme, Human, Hombre, Néphrologie, Nephrology, Nefrología, Pioglitazone, Pioglitazona, Rosiglitazone, Rosiglitazona, Traitement, Treatment, Tratamiento, Urologie, Urology, and Urología
Background The use of pioglitazone, a thiazolidinedione (TZD), may increase the risk of bladder cancer in patients with type 2 diabetes. In this study, we assessed the risk of bladder cancer associated with the use ofTZDs and between pioglitazone and rosiglitazone, an alternative TZD. Methods We conducted a retrospective cohort study of patients with type 2 diabetes mellitus who initiated treatment with aTZD (n = 18 459 patients) or a sulfonylurea (SU) (n = 41 396 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 theTZD 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. Results We identified 60 incident bladder cancers in theTZD 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 ofTZD vs SU therapy (≥5 years of use, HR = 3.25, 95% CI = 1.08 to 9.71) and among those with the longest time since initiation of therapy (≥5 years 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 (Ptrend < .001) and rosiglitazone (Ptrend = .006). Comparison of pioglitazone to rosiglitazone use did not demonstrate difference in cancer risk (P = .49). Conclusion Long-term TZD therapy (≥5 years) in patients with type 2 diabetes may be associated with an increased risk of bladder cancer, which may be common to all TZDs.