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

K. Hermansen*, T. A. Bækdal, M. Düring, A. Pietraszek, L. S. Mortensen, H. Jørgensen, A. Flint

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

116 Citations (Scopus)

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.

Original languageEnglish
JournalDiabetes, Obesity and Metabolism
Volume15
Issue number11
Pages (from-to)1040-1048
Number of pages9
ISSN1462-8902
DOIs
Publication statusPublished - Nov 2013
Externally publishedYes

Keywords

  • Antidiabetic drug
  • GLP-1 analogue
  • Lipid-lowering therapy
  • Phase I-II study
  • Randomized trial
  • Type II diabetes

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