title: Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial.
abstract: BACKGROUND
  Dulaglutide and liraglutide, both glucagon-like peptide-1 (GLP-1) receptor agonists, improve glycaemic control and reduce weight in patients with type 2 diabetes. In a head-to-head trial, we compared the safety and efficacy of once-weekly dulaglutide with that of once-daily liraglutide in metformin-treated patients with uncontrolled type 2 diabetes.
  
  
  METHODS
  We did a phase 3, randomised, open-label, parallel-group study at 62 sites in nine countries between June 20, 2012, and Nov 25, 2013. Patients with inadequately controlled type 2 diabetes receiving metformin (≥1500 mg/day), aged 18 years or older, with glycated haemoglobin (HbA1c) 7·0% or greater (≥53 mmol/mol) and 10·0% or lower (≤86 mmol/mol), and body-mass index 45 kg/m(2) or lower were randomly assigned to receive once-weekly dulaglutide (1·5 mg) or once-daily liraglutide (1·8 mg). Randomisation was done according to a computer-generated random sequence with an interactive voice response system. Participants and investigators were not masked to treatment allocation. The primary outcome was non-inferiority (margin 0·4%) of dulaglutide compared with liraglutide for change in HbA1c (least-squares mean change from baseline) at 26 weeks. Safety data were collected for a further 4 weeks' follow-up. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01624259.
  
  
  RESULTS
  We randomly assigned 599 patients to receive once-weekly dulaglutide (299 patients) or once-daily liraglutide (300 patients). 269 participants in each group completed treatment at week 26. Least-squares mean reduction in HbA1c was -1·42% (SE 0·05) in the dulaglutide group and -1·36% (0·05) in the liraglutide group. Mean treatment difference in HbA1c was -0·06% (95% CI -0·19 to 0·07, pnon-inferiority<0·0001) between the two groups. The most common gastrointestinal adverse events were nausea (61 [20%] in dulaglutide group vs 54 [18%] in liraglutide group), diarrhoea (36 [12%] vs 36 [12%]), dyspepsia (24 [8%] vs 18 [6%]), and vomiting (21 [7%] vs 25 [8%]), with similar rates of study or study drug discontinuation because of adverse events between the two groups (18 [6%] in each group). The hypoglycaemia rate was 0·34 (SE 1·44) and 0·52 (3·01) events per patient per year, respectively, and no severe hypoglycaemia was reported.
  
  
  CONCLUSIONS
  Once-weekly dulaglutide is non-inferior to once-daily liraglutide for least-squares mean reduction in HbA1c, with a similar safety and tolerability profile.
  
  
  BACKGROUND
  Eli Lilly and Company.
authors.affiliation: The Ohio State University, Columbus, OH, USA. Electronic address: kathleen.dungan@osumc.edu.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Dungan
authors.affiliation: Clínica Juaneda, Endocrinología, Palma de Mallorca, Spain.
authors.forename: Santiago Tofé
authors.initials: ST
authors.lastname: Povedano
authors.affiliation: Profil Mainz GmbH & Co KG, Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Forst
authors.affiliation: Universidad Autónoma de Nuevo León, Monterrey, NL, Mexico.
authors.forename: José G González
authors.initials: JG
authors.lastname: González
authors.affiliation: Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Atisso
authors.affiliation: Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Whitney
authors.initials: W
authors.lastname: Sealls
authors.affiliation: Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Jessie L
authors.initials: JL
authors.lastname: Fahrbach
mesh_terms: D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005215:Fasting / Q000097:blood; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004763:Glucagon-Like Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D000069450:Liraglutide; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D000069450:Liraglutide; D008687:Metformin; D011993:Recombinant Fusion Proteins; C555680:dulaglutide