The Once-Daily Human Glucagon-Like Peptide-1 (GLP-1) Analog Liraglutide Improves Postprandial Glucose Levels in Type 2 Diabetes Patients

Introduction: Fasting and postprandial plasma glucose (FPG, PPG) control are both necessary to achieve glycosylated hemoglobin (HbA(1c)) regulation goals. Liraglutide, based on its glucagon-like peptide 1 (GLP-1)-mediated pharmacology and pharmacokinetics may reduce HbA(1c) through both FPG and PPG levels. The objective of the present study was to investigate the effect of once-daily liraglutide (0.6, 1.2, and 1.8 mg) at steady state on FPG, PPG, postprandial insulin, and gastric emptying. Methods: Eighteen subjects with type 2 diabetes, aged 18-70 years, with a body mass index of 18.5-40 kg/m(2) and HbA(1c) of 7.0%-9.5% were included in this single-centre, randomized, placebo-controlled, double-blind, two-period, cross over trial. Patients were randomized into two groups (A or B). Group A received once-daily liraglutide for 3 weeks, followed by a 3-4-week washout period and 3 weeks of once-daily placebo. Group B was treated as for Group A, but treatment periods were reversed (ie, placebo followed by liraglutide). A meal test was performed at steady-state liraglutide/placebo doses of 0.6, 1.2, and 1.8 mg/day. Plasma glucose, insulin, and paracetamol (acetaminophen) concentrations (to assess gastric emptying) were measured pre- and postmeal. Results: PPG levels significantly decreased (P<0.001) after all three liraglutide doses when compared with placebo. This decrease was also apparent when corrected for baseline (incremental excursions), with the exception of average incremental increase calculated as area under the concentration curve (AUC) over the fasting value from time zero to 5 hours (iAUC(0-5h)/5 hours) after liraglutide 0.6 mg, where there was a trend to decrease (P=0.082). In addition, FPG levels significantly decreased at all three liraglutide dose levels when compared to placebo (P<0.001). Fasting and postprandial insulin levels significantly increased with liraglutide versus placebo at all doses studied (P<0.001). A significant delay in gastric emptying during the first hour postmeal was observed at the two highest liraglutide doses versus placebo. Conclusion: In addition to lowering FPG levels, liraglutide improves PPG levels (absolute and incremental) possibly by both stimulating postprandial insulin secretion and delaying gastric emptying.