Vildagliptin therapy reduces postprandial intestinal triglyceride-rich lipoprotein particles in patients with type 2 diabetes

Abstract

Aims/hypothesis: We assessed the effects of vildagliptin, a novel dipeptidyl peptidase IV inhibitor, on postprandial lipid and lipoprotein metabolism in patients with type 2 diabetes. Subjects, materials and methods: This was a single-centre, randomised, double-blind study in drug-naive patients with type 2 diabetes. Patients received vildagliptin (50 mg twice daily, n=15) or placebo (n=16) for 4 weeks. Triglyceride, cholesterol, lipoprotein, glucose, insulin, glucagon and glucagon-like peptide-1 (GLP-1) responses to a fat-rich mixed meal were determined for 8 h postprandially before and after 4 weeks of treatment. Results: Relative to placebo, 4 weeks of treatment with vildagliptin decreased the AUC0-8h for total trigyceride by 22±11% (p=0.037), the incremental AUC0-8h (IAUC0-8h) for total triglyceride by 85±47% (p=0.065), the AUC0-8h for chylomicron triglyceride by 65±19% (p=0.001) and the IAUC0-8h for chylomicron triglyceride by 91±28% (p=0.002). This was associated with a decrease in chylomicron apolipoprotein B-48 (AUC0-8h, -1.0±0.5 mg l-1 h, p=0.037) and chylomicron cholesterol (AUC0-8h, -0.14± 0.07 mmol l-1 h, p=0.046). Consistent with previous studies, 4 weeks of treatment with vildagliptin also increased intact GLP-1, suppressed inappropriate glucagon secretion, decreased fasting and postprandial glucose, and decreased HbA1c from a baseline of 6.7% (change, -0.4±0.1%, p<0.001), all relative to placebo. Conclusions/ interpretation: Treatment with vildagliptin for 4 weeks improves postprandial plasma triglyceride and apolipoprotein B-48-containing triglyceride-rich lipoprotein particle metabolism after a fat-rich meal. The mechanisms underlying the effects of this dipeptidyl peptidase IV inhibitor on postprandial lipid metabolism remain to be explored. © Springer-Verlag 2006.