title: Pioglitazone use and risk of bladder cancer: population based cohort study.
abstract: OBJECTIVE
  To determine whether pioglitazone compared with other antidiabetic drugs is associated with an increased risk of bladder cancer in people with type 2 diabetes.
  
  
  METHODS
  Population based cohort study.
  
  
  METHODS
  General practices contributing data to the United Kingdom Clinical Practice Research Datalink.
  
  
  METHODS
  A cohort of 145,806 patients newly treated with antidiabetic drugs between 1 January 2000 and 31 July 2013, with follow-up until 31 July 2014.
  
  
  METHODS
  The use of pioglitazone was treated as a time varying variable, with use lagged by one year for latency purposes. Cox proportional hazards models were used to estimate adjusted hazard ratios with 95% confidence intervals of incident bladder cancer associated with pioglitazone overall and by both cumulative duration of use and cumulative dose. Similar analyses were conducted for rosiglitazone, a thiazolidinedione not previously associated with an increased risk of bladder cancer.
  
  
  RESULTS
  The cohort generated 689,616 person years of follow-up, during which 622 patients were newly diagnosed as having bladder cancer (crude incidence 90.2 per 100,000 person years). Compared with other antidiabetic drugs, pioglitazone was associated with an increased risk of bladder cancer (121.0 v 88.9 per 100,000 person years; hazard ratio 1.63, 95% confidence interval 1.22 to 2.19). Conversely, rosiglitazone was not associated with an increased risk of bladder cancer (86.2 v 88.9 per 100,000 person years; 1.10, 0.83 to 1.47). Duration-response and dose-response relations were observed for pioglitazone but not for rosiglitazone.
  
  
  CONCLUSIONS
  The results of this large population based study indicate that pioglitazone is associated with an increased risk of bladder cancer. The absence of an association with rosiglitazone suggests that the increased risk is drug specific and not a class effect.
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal.
authors.forename: Marco
authors.initials: M
authors.lastname: Tuccori
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal Division of Clinical Epidemiology, McGill University.
authors.forename: Kristian B
authors.initials: KB
authors.lastname: Filion
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Hui
authors.initials: H
authors.lastname: Yin
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada Division of Endocrinology, Jewish General Hospital, Montreal.
authors.forename: Oriana H
authors.initials: OH
authors.lastname: Yu
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal Department of Pediatrics, McGill University, Montreal Research Institute of the McGill University Health Centre, Montreal.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Platt
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada Department of Oncology, McGill University laurent.azoulay@mcgill.ca.
authors.forename: Laurent
authors.initials: L
authors.lastname: Azoulay
mesh_terms: D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D058006:General Practice / Q000706:statistics & numerical data; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D012307:Risk Factors; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000009:adverse effects*; D006113:United Kingdom / Q000453:epidemiology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000453:epidemiology
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077205:Pioglitazone