title: Efficacy and safety of once-weekly dulaglutide in combination with sulphonylurea and/or biguanide compared with once-daily insulin glargine in Japanese patients with type 2 diabetes: a randomized, open-label, phase III, non-inferiority study.
abstract: OBJECTIVE
  To evaluate 0.75 mg of dulaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, compared with once-daily insulin glargine for glycaemic control in Japanese patients with type 2 diabetes (T2D).
  
  
  METHODS
  In this phase III, randomized, open-label, parallel-group, 26-week study, 361 patients with inadequately controlled T2D receiving sulphonylureas and/or biguanides, aged ≥20 years, with glycated haemoglobin (HbA1c) levels 7.0-10.0% (53-86 mmol/mol), inclusive, were randomized (1 : 1) to receive dulaglutide or glargine. Participants and investigators were not masked to treatment allocation. The primary measure was change from baseline in HbA1c at 26 weeks, analysed using a mixed-effects model for repeated measures, with a predefined non-inferiority margin of 0.4%.
  
  
  RESULTS
  At week 26, least-squares (LS) mean (standard error) reductions in HbA1c were -1.44 (0.05)% [-15.74 (0.55) mmol/mol] in the dulaglutide group and -0.90 (0.05)% [-9.84 (0.55) mmol/mol] in the glargine group. The mean between-group treatment difference in HbA1c was -0.54% (95% CI -0.67, -0.41) [-5.90 mmol/mol (95% CI -7.32, -4.48)]; p < 0.001. Dulaglutide significantly reduced body weight compared with glargine at week 26 (LS mean difference -1.42 kg, 95% CI -1.89, -0.94; p < 0.001). The most frequent adverse events with dulaglutide treatment were nasopharyngitis and gastrointestinal symptoms. The incidence of hypoglycaemia was significantly lower with dulaglutide [47/181 (26%)] compared with glargine [86/180 (48%)], p < 0.001.
  
  
  CONCLUSIONS
  In Japanese patients with T2D uncontrolled on sulphonylureas and/or biguanides, once-weekly dulaglutide was superior to once-daily glargine for reduction in HbA1c at 26 weeks. Although dulaglutide increased gastrointestinal symptoms, it was well tolerated, with an acceptable safety profile.
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Araki
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Inagaki
authors.affiliation: Division of Endocrinology, Metabolism, Hematological Science and Therapeutics, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tanizawa
authors.affiliation: Eli Lilly Japan K.K., Kobe, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Oura
authors.affiliation: Eli Lilly Japan K.K., Kobe, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Eli Lilly Japan K.K., Kobe, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Imaoka
mesh_terms: D000368:Aged; D001645:Biguanides / Q000008:administration & dosage*; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; 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*; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D000069036:Insulin Glargine / Q000008:administration & dosage*; D007564:Japan; D008297:Male; D008875:Middle Aged; D009304:Nasopharyngitis / Q000139:chemically induced; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D013453:Sulfonylurea Compounds / Q000008:administration & dosage*
chemical_list: D001645:Biguanides; D001786:Blood Glucose; D004763:Glucagon-Like Peptides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D000069036:Insulin Glargine; D011993:Recombinant Fusion Proteins; D013453:Sulfonylurea Compounds; C517652:hemoglobin A1c protein, human; C555680:dulaglutide
keywords: GLP-1 receptor agonist; dulaglutide; insulin glargine; type 2 diabetes