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.

AIMS: To evaluate dose-response efficacy and safety of once-daily human GLP-1 analog liraglutide in Japanese subjects with type 2 diabetes.

METHODS: Patients (226, treated with diet with/without OADs, mean HbA(1c) 8.30%, mean BMI 23.9kg/m(2)) were randomized after OAD discontinuation and washout to receive liraglutide 0.1, 0.3, 0.6 or 0.9mg once daily, or placebo in double-blind, parallel-group design for 14 weeks.

RESULTS: Liraglutide dose levels reduced HbA(1c) versus placebo (by 0.79%, 1.22%, 1.64% and 1.85%, respectively; p<0.0001 for linear contrast). Liraglutide 0.9mg/day resulted in 75% of patients achieving HbA(1c) <7.0% and 57% achieving HbA(1c) <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 2.5mmol/L), postprandial (0-3h) glucose excursion (up to 12.8mmol/(Lh)); and increased postprandial insulin secretion (up to 23.0microU/(mLh)) and beta-cell function as evaluated by HOMA-beta (up to around 20.0(microU/mL)/(mg/dL)). Body weight was unchanged; no development of liraglutide antibodies was detected.

CONCLUSIONS: Liraglutide was highly effective and well tolerated at doses up to 0.9mg/day in Japanese patients with type 2 diabetes, allowing glycemic control without weight gain or hypoglycemia.