Abstract
AIMS/HYPOTHESIS: Previous studies have suggested an increased risk of bladder cancer with pioglitazone exposure. We aimed to investigate the association between pioglitazone exposure and bladder cancer in France. METHODS: This cohort study involved use of data from the French national health insurance information system (Système National d'Information Inter-régimes de l'Assurance Maladie; SNIIRAM) linked with the French hospital discharge database (Programme de Médicalisation des Systèmes d'Information; PMSI). The cohort included patients aged 40 to 79 years who filled a prescription for a glucose-lowering drug in 2006. The cohort was followed for up to 42 months. Pioglitazone exposure was modelled as a time-dependent variable and defined by having filled at least two prescriptions over a 6-month period. Incident cases of bladder cancer were identified by a discharge diagnosis of bladder cancer combined with specific aggressive treatment. Statistical analyses involved a multivariate Cox model adjusted for age, sex and exposure to other glucose-lowering drugs. RESULTS: The cohort included 1,491,060 diabetic patients, 155,535 of whom were exposed to pioglitazone. We found 175 cases of bladder cancer among exposed patients and 1,841 among non-exposed patients. Incidence rates were 49.4 and 42.8 per 100,000 person-years, respectively. Pioglitazone exposure was significantly associated with bladder cancer incidence (adjusted HR 1.22 [95% CI 1.05, 1.43]). We observed a dose-effect relationship, with a significantly increased risk for high cumulative doses (≥ 28,000 mg, adjusted HR 1.75 [95% CI 1.22, 2.50]) and long duration of exposure (≥ 24 months, adjusted HR 1.36 [1.04, 1.79]). CONCLUSIONS/INTERPRETATION: In this cohort of diabetic patients from France, pioglitazone exposure was significantly associated with increased risk of bladder cancer.