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.
OBJECTIVE
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.
Seino
Y
Y
Kansai Electric Power Hospital, 2-1-7 Fukushima Fukushima-ku Osaka-shi, 553-0003 Osaka, Japan. seino.yutaka@e2.kepco.co.jp
Rasmussen
M F
MF
Zdravkovic
M
M
Kaku
K
K
D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007564:Japan; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D012449:Safety
D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069450:Liraglutide