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

Abstract

Aims: Postprandial triglyceridaemia is a risk factor for cardiovascular disease (CVD). This study investigated the effects of steady-state liraglutide 1.8mg versus placebo on postprandial plasma lipid concentrations after 3weeks of treatment in patients with type 2 diabetes mellitus (T2DM). Methods: In a cross-over trial, patients with T2DM (n=20, 18-75years, BMI 18.5-40kg/m2) were randomized to once-daily subcutaneous liraglutide (weekly dose escalation from 0.6 to 1.8mg) and placebo. After each 3-week period, a standardized fat-rich meal was provided, and the effects of liraglutide on triglyceride (primary endpoint AUC0-8h), apolipoprotein B48, non-esterified fatty acids, glycaemic responses and gastric emptying were assessed. ClinicalTrials.gov ID: NCT00993304. Funding: Novo Nordisk A/S. Results: After 3weeks, mean postprandial triglyceride (AUC0-8h liraglutide/placebo treatment-ratio 0.72, 95% CI [0.62-0.83], p=0.0004) and apolipoprotein B48 (AUC0-8h ratio 0.65 [0.58-0.73], p<0.0001) significantly decreased with liraglutide 1.8mg versus placebo, as did iAUC0-8h and Cmax (p<0.001). No significant treatment differences were observed for non-esterified fatty acids. Mean postprandial glucose and glucagon AUC0-8h and Cmax 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 John Wiley & Sons Ltd 15 11 November 2013 10.1111/dom.12133 ORIGINAL ARTICLE ORIGINAL ARTICLES © 2013 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.