title: Association Between Incretin-Based Drugs and the Risk of Acute Pancreatitis.
abstract: OBJECTIVE
  The association between incretin-based drugs, such as dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists, and acute pancreatitis is controversial.
  
  
  OBJECTIVE
  To determine whether the use of incretin-based drugs, compared with the use of 2 or more other oral antidiabetic drugs, is associated with an increased risk of acute pancreatitis.
  
  
  METHODS
  A large, international, multicenter, population-based cohort study was conducted using combined health records from 7 participating sites in Canada, the United States, and the United Kingdom. An overall cohort of 1 532 513 patients with type 2 diabetes initiating the use of antidiabetic drugs between January 1, 2007, and June 30, 2013, was included, with follow-up until June 30, 2014.
  
  
  METHODS
  Current use of incretin-based drugs compared with current use of at least 2 oral antidiabetic drugs.
  
  
  METHODS
  Nested case-control analyses were conducted including hospitalized patients with acute pancreatitis matched with up to 20 controls on sex, age, cohort entry date, duration of treated diabetes, and follow-up duration. Hazard ratios (HRs) and 95% CIs for hospitalized acute pancreatitis were estimated and compared current use of incretin-based drugs with current use of 2 or more oral antidiabetic drugs. Secondary analyses were performed to assess whether the risk varied by class of drug (DPP-4 inhibitors and GLP-1 agonists) or by duration of use. Site-specific HRs were pooled using random-effects models.
  
  
  RESULTS
  Of 1 532 513 patients included in the analysis, 781 567 (51.0%) were male; mean age was 56.6 years. During 3 464 659 person-years of follow-up, 5165 patients were hospitalized for acute pancreatitis (incidence rate, 1.49 per 1000 person-years). Compared with current use of 2 or more oral antidiabetic drugs, current use of incretin-based drugs was not associated with an increased risk of acute pancreatitis (pooled adjusted HR, 1.03; 95% CI, 0.87-1.22). Similarly, the risk did not vary by drug class (DPP-4 inhibitors: pooled adjusted HR, 1.09; 95% CI, 0.86-1.22; GLP-1 agonists: pooled adjusted HR, 1.04; 95% CI, 0.81-1.35) and there was no evidence of a duration-response association.
  
  
  CONCLUSIONS
  In this large population-based study, use of incretin-based drugs was not associated with an increased risk of acute pancreatitis compared with other oral antidiabetic drugs.
authors.affiliation: Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, Canada2Department of Oncology, McGill University, Montreal, Quebec, Canada.
authors.forename: Laurent
authors.initials: L
authors.lastname: Azoulay
authors.affiliation: Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, Canada3Department of Medicine, McGill University, Montreal, Quebec, 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, Montreal, Quebec, Canada5The Research Institute of the McGill University Health Centre, Montreal, Quebec, 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, Manitoba, Canada7Department of Family Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Dahl
authors.affiliation: Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Colin R
authors.initials: CR
authors.lastname: Dormuth
authors.affiliation: Department of Medicine, Western University, London, Ontario, Canada.
authors.forename: Kristin K
authors.initials: KK
authors.lastname: Clemens
authors.affiliation: Department of Internal Medicine, University of Montreal Health Centre, Montreal, Quebec, Canada.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Durand
authors.affiliation: Health Quality Council, Saskatoon, Saskatchewan, Canada.
authors.forename: Nianping
authors.initials: N
authors.lastname: Hu
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
authors.forename: David N
authors.initials: DN
authors.lastname: Juurlink
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada13Institute of Health Policy, Management and Evaluation, University of Toronto, Ontario, Toronto.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Paterson
authors.affiliation: Manitoba Centre for Health Policy, Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada13Institute of Health Policy, Management and Evaluation, University of Toronto, Ontario, Toronto.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Targownik
authors.affiliation: Department of Family Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Tanvir C
authors.initials: TC
authors.lastname: Turin
authors.affiliation: Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, Canada3Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Ernst
authors.forename: Samy
authors.initials: S
authors.lastname: Suissa
authors.affiliation: Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Colin R
authors.initials: CR
authors.lastname: Dormuth
authors.forename: Brenda R
authors.initials: BR
authors.lastname: Hemmelgarn
authors.forename: Gary F
authors.initials: GF
authors.lastname: Teare
authors.forename: Patricia
authors.initials: P
authors.lastname: Caetano
authors.forename: Dan
authors.initials: D
authors.lastname: Chateau
authors.forename: David A
authors.initials: DA
authors.lastname: Henry
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada13Institute of Health Policy, Management and Evaluation, University of Toronto, Ontario, Toronto.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Paterson
authors.forename: Jacques
authors.initials: J
authors.lastname: LeLorier
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Levy
authors.affiliation: Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, Canada3Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Ernst
authors.affiliation: Departments of Pediatrics and of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada5The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Platt
authors.forename: Ingrid S
authors.initials: IS
authors.lastname: Sketris
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000819:agonists; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D054795:Incretins / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000139:chemically induced*; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D054795:Incretins; D052216:Glucagon-Like Peptide 1