1. Liraglutide suppresses postprandial triglyceride and apolipoprotein B48 elevations after a fat-rich meal in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, cross-over trial.
- Author
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Hermansen K, Bækdal TA, Düring M, Pietraszek A, Mortensen LS, Jørgensen H, and Flint A
- Subjects
- Aged, Body Mass Index, Cardiovascular Diseases complications, Cardiovascular Diseases epidemiology, Cross-Over Studies, Denmark epidemiology, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 complications, Double-Blind Method, Female, Gastric Emptying drug effects, Germany epidemiology, Glucagon-Like Peptide 1 adverse effects, Glucagon-Like Peptide 1 blood, Glucagon-Like Peptide 1 pharmacokinetics, Glucagon-Like Peptide 1 therapeutic use, Half-Life, Humans, Hyperlipidemias complications, Hyperlipidemias etiology, Hypoglycemic Agents adverse effects, Hypoglycemic Agents blood, Hypoglycemic Agents pharmacokinetics, Hypolipidemic Agents adverse effects, Hypolipidemic Agents blood, Hypolipidemic Agents pharmacokinetics, Lipids blood, Liraglutide, Male, Middle Aged, Obesity complications, Postprandial Period, Risk Factors, Cardiovascular Diseases prevention & control, Diabetes Mellitus, Type 2 drug therapy, Diet, High-Fat adverse effects, Glucagon-Like Peptide 1 analogs & derivatives, Hyperlipidemias prevention & control, Hypoglycemic Agents therapeutic use, Hypolipidemic Agents therapeutic use
- Abstract
Aims: Postprandial triglyceridaemia is a risk factor for cardiovascular disease (CVD). This study investigated the effects of steady-state liraglutide 1.8 mg versus placebo on postprandial plasma lipid concentrations after 3 weeks of treatment in patients with type 2 diabetes mellitus (T2DM)., Methods: In a cross-over trial, patients with T2DM (n = 20, 18-75 years, BMI 18.5-40 kg/m²) were randomized to once-daily subcutaneous liraglutide (weekly dose escalation from 0.6 to 1.8 mg) and placebo. After each 3-week period, a standardized fat-rich meal was provided, and the effects of liraglutide on triglyceride (primary endpoint AUC(0-8h)), apolipoprotein B48, non-esterified fatty acids, glycaemic responses and gastric emptying were assessed. ClinicalTrials.gov ID: NCT00993304., Funding: Novo Nordisk A/S., Results: After 3 weeks, mean postprandial triglyceride (AUC(0-8h) liraglutide/placebo treatment-ratio 0.72, 95% CI [0.62-0.83], p = 0.0004) and apolipoprotein B48 (AUC(0-8h) ratio 0.65 [0.58-0.73], p < 0.0001) significantly decreased with liraglutide 1.8 mg versus placebo, as did iAUC(0-8h) and C(max) (p < 0.001). No significant treatment differences were observed for non-esterified fatty acids. Mean postprandial glucose and glucagon AUC(0-8h) and C(max) were significantly reduced with liraglutide versus placebo. Postprandial gastric emptying rate [assessed by paracetamol absorption (liquid phase) and the ¹³C-octanoate breath test (solid phase)] displayed no treatment differences. Mean low-density lipoprotein and total cholesterol decreased significantly with liraglutide versus placebo., Conclusions: Liraglutide treatment in patients with T2DM significantly reduced postprandial excursions of triglyceride and apolipoprotein B48 after a fat-rich meal, independently of gastric emptying. Results indicate liraglutide's potential to reduce CVD risk via improvement of postprandial lipaemia., (© 2013 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)
- Published
- 2013
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