title: Placebo-controlled, randomized trial of the addition of once-weekly glucagon-like peptide-1 receptor agonist dulaglutide to titrated daily insulin glargine in patients with type 2 diabetes (AWARD-9).
abstract: To compare the addition of weekly dulaglutide vs the addition of placebo to titrated glargine in patients with type 2 diabetes (T2D) with sub-optimum glycated haemoglobin (HbA1c) concentration.
  
  
  
  Patients (N = 300) from this phase III, double-blind, parallel-arm, placebo-controlled study were randomized to weekly subcutaneous injections of dulaglutide 1.5 mg or placebo with titrated daily glargine (mean ± standard deviation baseline dose: 39 ± 22 U), with or without metformin (≥1500 mg/d). The primary endpoint was superiority of dulaglutide/glargine to placebo/glargine with regard to change from baseline in HbA1c level at 28 weeks.
  
  
  
  Least squares (LS) mean ± standard error (s.e.) HbA1c changes from baseline were -1.44 ± 0.09% (-15.74 ± 0.98 mmol/mol) with dulaglutide/glargine and -0.67 ± 0.09% (-7.32 ± 0.98 mmol/mol) with placebo/glargine at 28 weeks (LS mean difference [95% confidence interval] -0.77% [-0.97, -0.56]; P < .001). Body weight decreased with dulaglutide/glargine and increased with placebo/glargine (LS mean difference: -2.41 ± 0.39 kg; P < .001). Increases from baseline in mean glargine dose were significantly smaller with dulaglutide/glargine vs placebo/glargine (13 ± 2 U [0.1 ± 0.02 U/kg] vs 26 ± 2 U [0.3 ± 0.02 U/kg], respectively; P < .001; LS mean ± s.e. final dose: dulaglutide/glargine, 51 ± 2 U; placebo/glargine, 65 ± 2 U). The hypoglycaemia rate (≤3.9 mmol/L threshold) was 7.69 ± 15.15 and 8.56 ± 16.13 events/patient/year, respectively (P = .488). One episode of severe hypoglycaemia occurred in the dulaglutide/glargine group. Common gastrointestinal adverse events with dulaglutide were nausea (12.0%), diarrhoea (11.3%) and vomiting (6.0%).
  
  
  
  Weekly dulaglutide 1.5 mg added to basal insulin is an efficacious and well tolerated treatment option for patients with T2D.
authors.affiliation: Unit of Endocrinology and Diabetes, University Campus Bio-Medico, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pozzilli
authors.affiliation: Centre of Immunobiology, Barts and the London School of Medicine, Queen Mary University of London, UK.
authors.forename: Paul
authors.identifier: 0000-0002-0485-8050
authors.initials: P
authors.lastname: Norwood
authors.affiliation: Valley Endocrine and Research, Fresno, California.|Hospital Universitario Quirón Salud Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid.
authors.forename: Esteban
authors.initials: E
authors.lastname: Jódar
authors.affiliation: University of Leicester, Diabetes Research Centre, Leicester, UK.
authors.forename: Melanie J
authors.identifier: 0000-0002-9987-9371
authors.initials: MJ
authors.lastname: Davies
authors.affiliation: Eli Lilly and Company, Budapest, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Ivanyi
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Honghua
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: D Bradley
authors.initials: DB
authors.lastname: Woodward
authors.affiliation: Eli Lilly and Company, Vienna, Austria.
authors.forename: Zvonko
authors.identifier: 0000-0002-6746-901X
authors.initials: Z
authors.lastname: Milicevic
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor / Q000037:antagonists & inhibitors*; D004763:Glucagon-Like Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D054795:Incretins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D000069036:Insulin Glargine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D054795:Incretins; D000069036:Insulin Glargine; D011993:Recombinant Fusion Proteins; C517652:hemoglobin A1c protein, human; C555680:dulaglutide
keywords: 
  AWARD-9; GLP-1 receptor agonists; dulaglutide; insulin glargine; type 2 diabetes