title: Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5).
abstract: OBJECTIVE
  To compare the efficacy and safety of two doses of once-weekly dulaglutide, a glucagon-like peptide 1 receptor agonist, to sitagliptin in uncontrolled, metformin-treated patients with type 2 diabetes. The primary objective was to compare (for noninferiority and then superiority) dulaglutide 1.5 mg versus sitagliptin in change from baseline in glycosylated hemoglobin A1c (HbA1c) at 52 weeks.
  
  
  METHODS
  This multicenter, adaptive, double-blind, parallel-arm study randomized patients (N = 1,098; mean baseline age 54 years; HbA1c 8.1% [65 mmol/mol]; weight 86.4 kg; diabetes duration 7 years) to dulaglutide 1.5 mg, dulaglutide 0.75 mg, sitagliptin 100 mg, or placebo (placebo-controlled period up to 26 weeks). The treatment period lasted 104 weeks, with 52-week primary end point data presented.
  
  
  RESULTS
  The mean HbA1c changes to 52 weeks were (least squares mean ± SE): -1.10 ± 0.06% (-12.0 ± 0.7 mmol/mol), -0.87 ± 0.06% (9.5 ± 0.7 mmol/mol), and -0.39 ± 0.06% (4.3 ± 0.7 mmol/mol) for dulaglutide 1.5 mg, dulaglutide 0.75 mg, and sitagliptin, respectively. Both dulaglutide doses were superior to sitagliptin (P < 0.001, both comparisons). No events of severe hypoglycemia were reported. Mean weight changes to 52 weeks were greater with dulaglutide 1.5 mg (-3.03 ± 0.22 kg) and dulaglutide 0.75 mg (-2.60 ± 0.23 kg) compared with sitagliptin (-1.53 ± 0.22 kg) (P < 0.001, both comparisons). The most common gastrointestinal treatment-emergent adverse events in dulaglutide 1.5- and 0.75-mg arms were nausea, diarrhea, and vomiting.
  
  
  CONCLUSIONS
  Both dulaglutide doses demonstrated superior glycemic control versus sitagliptin at 52 weeks with an acceptable tolerability and safety profile.
authors.affiliation: Diabeteszentrum Bad Lauterberg, Bad Lauterberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Nauck
authors.affiliation: Upstate Medical University, Syracuse, NY.
authors.forename: Ruth S
authors.initials: RS
authors.lastname: Weinstock
authors.affiliation: Emory University, Atlanta, GA.
authors.forename: Guillermo E
authors.initials: GE
authors.lastname: Umpierrez
authors.affiliation: Diabetology, Nutrition, and Metabolic Disorders, University of Lorraine, Brabois Hospital, Vandoeuvre-Les-Nancy, FranceCenter of Clinical Investigation ILCV, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-Les-Nancy, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Guerci
authors.affiliation: Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Skrivanek
authors.affiliation: Lilly Diabetes, Eli Lilly and Company, Vienna, Austria milicevic_zvonko@lilly.com.
authors.forename: Zvonko
authors.initials: Z
authors.lastname: Milicevic
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use; D004763:Glucagon-Like Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D000068900:Sitagliptin Phosphate; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D008687:Metformin; D011719:Pyrazines; D011993:Recombinant Fusion Proteins; D000068900:Sitagliptin Phosphate; D014230:Triazoles; C555680:dulaglutide
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