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

Diabetologia. 2006 Sep;49(9):2049-57. doi: 10.1007/s00125-006-0340-2. Epub 2006 Jul 1.

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 AUC(0-8h) for total trigyceride by 22+/-11% (p=0.037), the incremental AUC(0-8h) (IAUC(0-8h)) for total triglyceride by 85+/-47% (p=0.065), the AUC(0-8h) for chylomicron triglyceride by 65+/-19% (p=0.001) and the IAUC(0-8h) for chylomicron triglyceride by 91+/-28% (p=0.002). This was associated with a decrease in chylomicron apolipoprotein B-48 (AUC(0-8h), -1.0+/-0.5 mg l(-1) h, p=0.037) and chylomicron cholesterol (AUC(0-8h), -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 HbA(1c) 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / chemistry
  • Adamantane / therapeutic use
  • Apolipoprotein B-48 / blood
  • Apolipoprotein B-48 / metabolism
  • Blood Glucose / analysis
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors
  • Double-Blind Method
  • Female
  • Glucagon / blood
  • Glucagon-Like Peptide 1 / blood
  • Humans
  • Insulin / blood
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects*
  • Lipids / blood
  • Lipoproteins / blood
  • Lipoproteins / chemistry
  • Lipoproteins / metabolism*
  • Male
  • Middle Aged
  • Nitriles / chemistry
  • Nitriles / therapeutic use*
  • Postprandial Period
  • Pyrrolidines / chemistry
  • Pyrrolidines / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Triglycerides / chemistry*
  • Vildagliptin

Substances

  • Apolipoprotein B-48
  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Insulin
  • Lipids
  • Lipoproteins
  • Nitriles
  • Pyrrolidines
  • Triglycerides
  • Glucagon-Like Peptide 1
  • Glucagon
  • Vildagliptin
  • Adamantane