title: Monotherapy with the once weekly GLP-1 receptor agonist dulaglutide for 12 weeks in Japanese patients with type 2 diabetes: dose-dependent effects on glycaemic control in a randomised, double-blind, placebo-controlled study.
abstract: The aim of this study was to evaluate the dose-dependent effect of dulaglutide, a glucagon-like peptide-1 receptor agonist, on glycaemic control in Japanese patients with type 2 diabetes mellitus who were treated with diet/exercise or oral antidiabetic drug monotherapy. In this randomised, double-blind, placebo-controlled, parallel-group, 12-week study, patients received once weekly subcutaneous dulaglutide doses of 0.25, 0.5, or 0.75 mg (DU 0.25, DU 0.5, and DU 0.75, respectively) or placebo (n=36, 37, 35, and 37, respectively). The primary measure was change from baseline in glycated haemoglobin (HbA1c; %) at 12 weeks. Continuous variables were analysed using a mixed-effects model for repeated measures. Significant dose-dependent reductions in HbA1c were observed (least squares mean difference versus placebo [95% confidence interval]): DU 0.25=-0.72% (-0.95, -0.48), DU 0.5=-0.97% (-1.20, -0.73), and DU 0.75=-1.17% (-1.41, -0.93); p<0.001. Significant improvements in plasma glucose (PG), both fasting and average 7-point self-monitored blood glucose, were also observed with dulaglutide versus placebo (p<0.001). Dulaglutide was well-tolerated. Gastrointestinal adverse events (AEs) were more common in dulaglutide-treated patients, with nausea the most frequent (8 [5.5%]). Few dulaglutide-treated patients discontinued due to AEs (4 [3.7%]), and no serious AEs related to study medication occurred. Three patients (DU 0.5=1 and DU 0.75=2) reported asymptomatic hypoglycaemia (PG ≤70 mg/dL). The observed dose-dependent reduction in HbA1c and acceptable safety profile support further clinical development of dulaglutide for treatment of type 2 diabetes mellitus in Japan.
authors.affiliation: Department of Endocrinology & Metabolism, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Satoi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Imaoka
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018027:Receptors, Glucagon / Q000819:agonists*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D018027:Receptors, Glucagon; D011993:Recombinant Fusion Proteins; D004763:Glucagon-Like Peptides; C555680:dulaglutide