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

AimsPostprandial 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). MethodsIn a cross-over trial, patients with T2DM (n=20, 18-75years, BMI 18.5-40kg/m(2)) 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 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. ResultsAfter 3weeks, 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 1.8mg 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 C-13-octanoate breath test (solid phase)] displayed no treatment differences. Mean low-density lipoprotein and total cholesterol decreased significantly with liraglutide versus placebo. ConclusionsLiraglutide 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.