title: Once-weekly glucagon-like peptide-1 receptor agonist dulaglutide is non-inferior to once-daily liraglutide and superior to placebo in Japanese patients with type 2 diabetes: a 26-week randomized phase III study.
abstract: OBJECTIVE
  To examine the efficacy and safety of once-weekly dulaglutide monotherapy (0.75 mg) compared with placebo and once-daily liraglutide (0.9 mg) in Japanese patients with type 2 diabetes.
  
  
  METHODS
  This was a phase III, 52-week (26-week primary endpoint), randomized, double-blind, placebo-controlled, open-label comparator (liraglutide) trial comparing 492 Japanese patients with type 2 diabetes (dulaglutide, n = 281; liraglutide, n = 141; and placebo, n = 70) who were aged ≥20 years. Patients and investigators were blinded to treatment assignment for dulaglutide and placebo but not for liraglutide. The primary objective evaluated the superiority of dulaglutide versus placebo on change from baseline in glycated haemoglobin (HbA1c) at 26 weeks. Analyses were performed on the full analysis set.
  
  
  RESULTS
  At 26 weeks, once-weekly dulaglutide was superior to placebo and non-inferior to once-daily liraglutide for HbA1c change from baseline [least squares mean difference: dulaglutide vs placebo -1.57% (95% confidence interval -1.79 to -1.35); dulaglutide vs liraglutide -0.10% (95% confidence interval -0.27 to 0.07)]. The most frequently reported adverse events were nasopharyngitis, constipation, diarrhoea, nausea, abdominal distension and decreased appetite; only decreased appetite was different between the dulaglutide and liraglutide groups [dulaglutide, n = 2 (0.7%); liraglutide, n = 8 (5.8%); p = 0.003]. Nine (1.8%) patients experienced hypoglycaemia [dulaglutide, n = 6 (2.1%); liraglutide, n = 2 (1.5%); placebo, n = 1 (1.4%)], with no event being severe.
  
  
  CONCLUSIONS
  In Japanese patients with type 2 diabetes, once-weekly dulaglutide (0.75 mg) was superior to placebo and non-inferior to once-daily liraglutide (0.9 mg) for reduction in HbA1c at 26 weeks. Dulaglutide was safe and well tolerated.
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Miyagawa
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Diabetes, Endocrinology, Metabolism and Rheumatology, Tokyo Medical University, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Odawara
authors.affiliation: Department of Comprehensive Metabology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takamura
authors.affiliation: Eli Lilly Japan K.K, Kobe, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Iwamoto
authors.affiliation: Eli Lilly Japan K.K, Kobe, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takita
authors.affiliation: Eli Lilly Japan K.K, Kobe, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Imaoka
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D004763:Glucagon-Like Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D007564:Japan; D000069450:Liraglutide / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D004763:Glucagon-Like Peptides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D000069450:Liraglutide; D011993:Recombinant Fusion Proteins; C517652:hemoglobin A1c protein, human; C555680:dulaglutide
keywords: GLP-1 receptor agonist; dulaglutide; liraglutide; placebo; type 2 diabetes