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

Authors


Correspondence to: Dr K. Hermansen, MD, Department of Medicine and Endocrinology MEA, Aarhus University Hospital, DK-8000 Aarhus, Denmark. E-mail: kjeld.hermansen@aarhus.rm.dk

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 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 3 weeks, 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 1.8 mg 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.

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