title: Assessment of Pancreas Safety in the Development Program of Once-Weekly GLP-1 Receptor Agonist Dulaglutide.
abstract: To assess the risk of acute pancreatitis during treatment with glucagon-like peptide 1 receptor agonist dulaglutide, placebo, and active comparators across phase 2/3 dulaglutide trials.
  
  
  
  A total of 6,005 patients with type 2 diabetes participated (dulaglutide groupN= 4,006 [dose range 0.1-3.0 mg]; active comparator group [metformin, sitagliptin, exenatide twice daily, insulin glargine]N= 1,541; placebo groupN= 703; 245 placebo-treated patients subsequently received dulaglutide or sitagliptin and were also included in these groups) for up to 104 weeks. The following events were adjudicated: investigator-reported pancreatitis, adverse events (AEs) of severe or serious abdominal pain of unknown etiology, and confirmed asymptomatic increases in pancreatic enzymes ≥3× the upper limit of normal range.
  
  
  
  Overall, 203 events from 151 patients underwent adjudication (dulaglutide groupn= 108; comparator group including placebon= 43). Acute pancreatitis was confirmed by adjudication in seven patients (dulaglutiden= 3, placebon= 1, sitagliptinn= 3). Exposure-adjusted incidence rates were as follows: dulaglutide group 0.85 patients/1,000 patient-years, placebo group 3.52 patients/1,000 patient-years, sitagliptin group 4.71 patients/1,000 patient-years. No events of pancreatitis were confirmed by adjudication in patients treated with exenatide twice daily, metformin, or glargine. Increases in median values of lipase and pancreatic amylase within the normal range were observed with all treatments except glargine. These changes were not associated with AEs.
  
  
  
  The exposure-adjusted incidence rate of acute pancreatitis in dulaglutide-treated patients was similar to the rates with placebo, with few reported cases during the entire program.
authors.affiliation: Division of Diabetology, Medical Department I, St. Josef-Hospital (Ruhr-Universität Bochum), Bochum, Germany.
authors.forename: Michael A
authors.identifier: 0000-0003-2455-0472
authors.initials: MA
authors.lastname: Nauck
authors.affiliation: Division of Gastroenterology, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Jean-Louis
authors.identifier: 0000-0002-6309-1603
authors.initials: JL
authors.lastname: Frossard
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL.
authors.forename: Jamie S
authors.identifier: 0000-0001-5109-9053
authors.initials: JS
authors.lastname: Barkin
authors.affiliation: Eli Lilly Canada, Toronto, Ontario, Canada.
authors.forename: Greg
authors.initials: G
authors.lastname: Anglin
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Hensley
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Kristine D
authors.identifier: 0000-0001-8490-7520
authors.initials: KD
authors.lastname: Harper
authors.affiliation: Eli Lilly and Company, Vienna, Austria milicevic_zvonko@lilly.com.
authors.forename: Zvonko
authors.identifier: 0000-0002-6746-901X
authors.initials: Z
authors.lastname: Milicevic
mesh_terms: D000208:Acute Disease; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D000077270:Exenatide; D005260:Female; D004763:Glucagon-Like Peptides / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D007141:Immunoglobulin Fc Fragments / Q000009:adverse effects* / Q000627:therapeutic use*; D000069036:Insulin Glargine / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D010195:Pancreatitis / Q000139:chemically induced*; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000009:adverse effects* / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate / Q000009:adverse effects / Q000627:therapeutic use; D014688:Venoms / Q000009:adverse effects / Q000627:therapeutic use; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014688:Venoms; D000069036:Insulin Glargine; D004763:Glucagon-Like Peptides; D008687:Metformin; D000077270:Exenatide; D000068900:Sitagliptin Phosphate; C555680:dulaglutide; D000097789:Glucagon-Like Peptide-1 Receptor Agonists