title: Efficacy and Safety of Once-Weekly Dulaglutide Versus Insulin Glargine in Patients With Type 2 Diabetes on Metformin and Glimepiride (AWARD-2).
abstract: OBJECTIVE
  This study compared the efficacy and safety of once-weekly dulaglutide, a glucagon-like peptide-1 receptor agonist, with daily insulin glargine, both combined with maximally tolerated doses of metformin and glimepiride in patients with type 2 diabetes. The primary objective was noninferiority of dulaglutide 1.5 mg to glargine in the HbA1c change from baseline at 52 weeks.
  
  
  METHODS
  In this 78-week, open-label study, 810 patients were randomized to dulaglutide 1.5 mg, dulaglutide 0.75 mg, or glargine.
  
  
  RESULTS
  The baseline mean ± SD HbA1c was 8.1 ± 1.0% (65.5 ± 10.8 mmol/mol). The least squares mean ± SE HbA1c change from baseline to the primary end point was -1.08 ± 0.06% (-11.8 ± 0.7 mmol/mol) for dulaglutide 1.5 mg, -0.76 ± 0.06% (-8.3 ± 0.7 mmol/mol) for dulaglutide 0.75 mg, and -0.63 ± 0.06% (-6.9 ± 0.7 mmol/mol) for glargine, with an end point mean ± SD dose of 29 ± 26 units (0.33 ± 0.24 units/kg), and a fasting plasma glucose (mean ± SD) of 118 ± 23 mg/dL from self-monitored plasma glucose. Statistical criteria for superiority were met with dulaglutide 1.5 mg and for noninferiority with dulaglutide 0.75 mg. More patients on dulaglutide 1.5 mg achieved HbA1c targets <7.0% (53 mmol/mol) versus glargine (P < 0.001). Body weight decreased with dulaglutide and increased with glargine. Total hypoglycemia rates were lower with dulaglutide; severe hypoglycemia was minimal. Increases in pancreatic enzymes were observed for dulaglutide. Incidence of nausea (15.4, 7.7, and 1.5%) and diarrhea (10.6, 9.2, and 5.7%) were more common with dulaglutide 1.5 mg and 0.75 mg than with glargine.
  
  
  CONCLUSIONS
  Once-weekly dulaglutide 1.5 mg, compared with daily insulin glargine without forced titration, demonstrated greater HbA1c reduction and weight loss, with a higher incidence of gastrointestinal adverse events and a lower risk of hypoglycemia.
authors.affiliation: University of Bari Aldo Moro, Bari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Giorgino
authors.affiliation: Evangelismos-Polyclinic, Athens General Hospital, Athens, Greece.
authors.forename: Marian
authors.initials: M
authors.lastname: Benroubi
authors.affiliation: Chang Gung Memorial Hospital, Taoyuan Hsien, Taiwan.
authors.forename: Jui-Hung
authors.initials: JH
authors.lastname: Sun
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Alan G
authors.initials: AG
authors.lastname: Zimmermann
authors.affiliation: Eli Lilly and Company, Neuilly-Sur-Seine Cedex, France pechtner_valeria@lilly.com.
authors.forename: Valeria
authors.initials: V
authors.lastname: Pechtner
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D004763:Glucagon-Like Peptides / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage*; D000069036:Insulin Glargine / Q000008:administration & dosage*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D004763:Glucagon-Like Peptides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D000069036:Insulin Glargine; D008687:Metformin; D011993:Recombinant Fusion Proteins; D013453:Sulfonylurea Compounds; C057619:glimepiride; C555680:dulaglutide