title: 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: OBJECTIVE
  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.
  
  
  BACKGROUND
  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.
authors.affiliation: Department of Medicine and Endocrinology MEA, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Hermansen
authors.forename: T A
authors.initials: TA
authors.lastname: Bækdal
authors.forename: M
authors.initials: M
authors.lastname: Düring
authors.forename: A
authors.initials: A
authors.lastname: Pietraszek
authors.forename: L S
authors.initials: LS
authors.lastname: Mortensen
authors.forename: H
authors.initials: H
authors.lastname: Jørgensen
authors.forename: A
authors.initials: A
authors.lastname: Flint
mesh_terms: D000368:Aged; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D018592:Cross-Over Studies; D003718:Denmark / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D005858:Germany / Q000453:epidemiology; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000209:etiology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D019518:Postprandial Period; D012307:Risk Factors
chemical_list: D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D008055:Lipids; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1
keywords: GLP-1 analogue; antidiabetic drug; lipid-lowering therapy; phase I-II study; randomized trial; type II diabetes