title: Use of incretin agents and risk of acute and chronic pancreatitis: A population-based cohort study.
abstract: To determine the association between the use of incretin agents (dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists) for the treatment of type 2 diabetes mellitus (T2DM) and the risk of any, acute and chronic pancreatitis.
  
  
  
  A population-based cohort study was conducted using data from the UK Clinical Practice Research Datalink (CPRD 2007-2012). A total of 182 428 adult patients with ≥1 non-insulin antidiabetic drug (NIAD) prescription were matched to control subjects without diabetes. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of pancreatitis in incretin-users (N = 28 370) compared with controls and with other NIAD users. Adjustments were made for lifestyle, disease and drug history. In a sensitivity analysis, a new-user design was used.
  
  
  
  Current incretin users had a 1.5-fold increased risk of any pancreatitis compared with NIAD users (adjusted HR 1.47, 95% CI 1.06-2.04). In incident current incretin users the risk of any and acute pancreatitis was increased 2.1- and 2.0-fold compared with NIAD users (adjusted HR 2.12, 95% CI 1.31-3.43 and adjusted HR 1.96, 95% CI 1.13-3.41), whereas there was no increased risk found for chronic pancreatitis.
  
  
  
  Incretin use was associated with an increased risk of any pancreatitis. Moreover, risk of any and acute pancreatitis was higher when applying a new-user design. We were not able to detect an association with chronic pancreatitis, but the number in this subgroup was small.
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands.|CAPHRI Care and Public Health Research Institute, Maastricht University Medical Centre+, Maastricht, The Netherlands.
authors.forename: Lotte M
authors.initials: LM
authors.lastname: Knapen
authors.affiliation: Department of Internal Medicine, VieCuri Medical Centre, Venlo, The Netherlands.|GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, The Netherlands.|Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.
authors.forename: Roy G P J
authors.initials: RG
authors.lastname: de Jong
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands.|CAPHRI Care and Public Health Research Institute, Maastricht University Medical Centre+, Maastricht, The Netherlands.|Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.
authors.forename: Johanna H M
authors.initials: JH
authors.lastname: Driessen
authors.affiliation: Department of Gastroenterology, Zuyderland Medical Centre, Heerlen, The Netherlands.
authors.forename: Yolande C
authors.initials: YC
authors.lastname: Keulemans
authors.affiliation: Department of Pharmacy, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Nielka P
authors.initials: NP
authors.lastname: van Erp
authors.affiliation: Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.
authors.forename: Marie L
authors.initials: ML
authors.lastname: De Bruin
authors.affiliation: Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.
authors.forename: Hubert G M
authors.initials: HG
authors.lastname: Leufkens
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands.|CAPHRI Care and Public Health Research Institute, Maastricht University Medical Centre+, Maastricht, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Croes
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands.|CAPHRI Care and Public Health Research Institute, Maastricht University Medical Centre+, Maastricht, The Netherlands.|Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.|MRC Lifecourse Epidemiology Unit, Southampton General Hospital, University of Southampton, Southampton, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: de Vries
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D054795:Incretins / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000453:epidemiology; D050500:Pancreatitis, Chronic / Q000453:epidemiology*; D016016:Proportional Hazards Models; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D054795:Incretins; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: acute pancreatitis; chronic pancreatitis; cohort studies; dipeptidyl peptidase-4 inhibitors; glucagon-like peptide-1 receptor agonists; incretin-based therapy; type 2 diabetes mellitus