Diabetes Pharmacotherapies and Bladder Cancer: A Medicare Epidemiologic Study

OBJECTIVE Patients with type II diabetes have an increased risk of bladder cancer and are commonly treated with thiazolidinediones and angiotensin receptor blockers (ARBs), which have been linked to cancer risk. We explored the relationship between use of one or both of these medication types and incident bladder cancer among diabetic patients (diabetics) enrolled in Medicare. RESEARCH DESIGN AND METHODS We constructed both a prevalent and incident retrospective cohort of pharmacologically treated prevalent diabetics enrolled in a Medicare fee-for-service plan using inpatient, outpatient (2003-2011) and prescription (2006-2011) administrative data. The association of incident bladder cancer with exposure to pioglitazone, rosiglitazone and ARBs was studied using muitivariable Cox's hazard models with time-dependent covariates in each of the two cohorts. RESULTS We identified 1,161,443 prevalent and 320,090 incident pharmacologically treated diabetics, among whom 4433 and 1159, respectively, developed incident bladder cancers. In the prevalent cohort mean age was 75.1 years, mean follow-up time was 38.0 months, 20.2% filled a prescription for pioglitazone during follow-up, 10.4% received rosiglitazone, 31.6% received an ARB and 8.0% received combined therapy with pioglitazone + ARB. We found a positive association between bladder cancer and duration of pioglitazone use in the prevalent cohort (P for trend = 0.008), with ≥24 months of pioglitazone exposure corresponding to a 16% (95% confidence interval 0-35%) increase in the incidence of bladder cancer compared to no use. There was a positive association between bladder cancer and rosiglitazone use for <24 months in the prevalent cohort, but no association with ARB use. There were no significant associations in the incident cohort. CONCLUSIONS We found that the incidence of bladder cancer increased with duration of pioglitazone use in a prevalent cohort of diabetics aged 65+ years residing in the USA, but not an incident cohort.