Dose-dependent improvement in glycemia with once-daily liraglutide without hypoglycemia or weight gain: A double-blind, randomized, controlled trial in Japanese patients with type 2 diabetes

AimsTo evaluate dose–response efficacy and safety of once-daily human GLP-1 analog liraglutide in Japanese subjects with type 2 diabetes.MethodsPatients (226, treated with diet with/without OADs, mean HbA1c 8.30%, mean BMI 23.9 kg/m2) were randomized after OAD discontinuation and washout to receive liraglutide 0.1, 0.3, 0.6 or 0.9 mg once daily, or placebo in double-blind, parallel-group design for 14 weeks.ResultsLiraglutide dose levels reduced HbA1c versus placebo (by 0.79%, 1.22%, 1.64% and 1.85%, respectively; p < 0.0001 for linear contrast). Liraglutide 0.9 mg/day resulted in 75% of patients achieving HbA1c <7.0% and 57% achieving HbA1c <6.5%. There were no major or minor hypoglycemic events. Liraglutide also reduced, with significant dose–response (each p < 0.0001 for linear contrast) versus placebo: fasting plasma glucose (up to 2.5 mmol/L), postprandial (0–3 h) glucose excursion (up to 12.8 mmol/(L h)); and increased postprandial insulin secretion (up to 23.0 μU/(mL h)) and beta-cell function as evaluated by HOMA-β (up to around 20.0 (μU/mL)/(mg/dL)). Body weight was unchanged; no development of liraglutide antibodies was detected.ConclusionsLiraglutide was highly effective and well tolerated at doses up to 0.9 mg/day in Japanese patients with type 2 diabetes, allowing glycemic control without weight gain or hypoglycemia.