title: Incretin based drugs and the risk of pancreatic cancer: international multicentre cohort study.
abstract: OBJECTIVE
  To determine whether the use of incretin based drugs compared with sulfonylureas is associated with an increased risk of incident pancreatic cancer in people with type 2 diabetes.
  
  
  METHODS
  Population based cohort.
  
  
  METHODS
  Large, international, multicentre study combining the health records from six participating sites in Canada, the United States, and the United Kingdom.
  
  
  METHODS
  A cohort of 972,384 patients initiating antidiabetic drugs between 1 January 2007 and 30 June 2013, with follow-up until 30 June 2014.
  
  
  METHODS
  Within each cohort we conducted nested case-control analyses, where incident cases of pancreatic cancer were matched with up to 20 controls on sex, age, cohort entry date, duration of treated diabetes, and duration of follow-up. Hazard ratios and 95% confidence intervals for incident pancreatic cancer were estimated, comparing use of incretin based drugs with use of sulfonylureas, with drug use lagged by one year for latency purposes. Secondary analyses assessed whether the risk varied by class (dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists) or by duration of use (cumulative duration of use and time since treatment initiation). Site specific hazard ratios were pooled using random effects models.
  
  
  RESULTS
  During 2,024,441 person years of follow-up (median follow-up ranging from 1.3 to 2.8 years; maximum 8 years), 1221 patients were newly diagnosed as having pancreatic cancer (incidence rate 0.60 per 1000 person years). Compared with sulfonylureas, incretin based drugs were not associated with an increased risk of pancreatic cancer (pooled adjusted hazard ratio 1.02, 95% confidence interval 0.84 to 1.23). Similarly, the risk did not vary by class and evidence of a duration-response relation was lacking.
  
  
  CONCLUSIONS
  In this large, population based study the use of incretin based drugs was not associated with an increased risk of pancreatic cancer compared with sulfonylureas. Although this potential adverse drug reaction will need to be monitored long term owing to the latency of the cancer, these findings provide some reassurance on the safety of incretin based drugs.
authors.affiliation: Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, H3T 1E2, Canada Department of Oncology, McGill University, Montreal, Canada laurent.azoulay@mcgill.ca.
authors.forename: Laurent
authors.initials: L
authors.lastname: Azoulay
authors.affiliation: Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, H3T 1E2, Canada Department of Medicine, McGill University, Montreal, Canada.
authors.forename: Kristian B
authors.initials: KB
authors.lastname: Filion
authors.affiliation: Departments of Pediatrics and of Epidemiology, Biostatistics, and Occupational Health, McGill University, and the Research Institute of the McGill University Health Centre, Montreal, Canada.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Platt
authors.affiliation: Manitoba Centre for Health Policy, Department of Community Health Sciences, University of Manitoba, Winnipeg, Canada and Department of Family Medicine, McMaster University, Hamilton, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Dahl
authors.affiliation: Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, Canada.
authors.forename: Colin R
authors.initials: CR
authors.lastname: Dormuth
authors.affiliation: Department of Medicine, Western University, London, Canada.
authors.forename: Kristin K
authors.initials: KK
authors.lastname: Clemens
authors.affiliation: Department of Internal Medicine, Centre Hospitalier de l'Université de Montréal, Montreal, Canada.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Durand
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, Canada.
authors.forename: David N
authors.initials: DN
authors.lastname: Juurlink
authors.affiliation: Manitoba Centre for Health Policy, Department of Community Health Sciences, University of Manitoba, Winnipeg, Canada and Department of Family Medicine, McMaster University, Hamilton, Canada Section of Gastroenterology, Division of Internal Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Targownik
authors.affiliation: Department of Family Medicine, University of Calgary, Calgary, Canada.
authors.forename: Tanvir C
authors.initials: TC
authors.lastname: Turin
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, Canada Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Paterson
authors.affiliation: Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, H3T 1E2, Canada Department of Medicine, McGill University, Montreal, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Ernst
mesh_terms: D000328:Adult; D000368:Aged; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D054795:Incretins / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013453:Sulfonylurea Compounds / Q000009:adverse effects; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D055815:Young Adult; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D054795:Incretins; D013453:Sulfonylurea Compounds; D000097789:Glucagon-Like Peptide-1 Receptor Agonists