Vildagliptin therapy reduces postprandial intestinal triglyceride-rich lipoprotein particles in patients with type 2 diabetes.
OBJECTIVE
We assessed the effects of vildagliptin, a novel dipeptidyl peptidase IV inhibitor, on postprandial lipid and lipoprotein metabolism in patients with type 2 diabetes.


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
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.
Matikainen
N
N
Division of Cardiology, Department of Medicine, Helsinki University Central Hospital and Biomedicum, Helsinki, Finland.
Mänttäri
S
S
Schweizer
A
A
Ulvestad
A
A
Mills
D
D
Dunning
B E
BE
Foley
J E
JE
Taskinen
M-R
MR
D000218:Adamantane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D053283:Apolipoprotein B-48 / Q000097:blood / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004311:Double-Blind Method; D005260:Female; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000737:chemistry / Q000627:therapeutic use*; D019518:Postprandial Period; D011759:Pyrrolidines / Q000737:chemistry / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000737:chemistry*; D000077597:Vildagliptin
D053283:Apolipoprotein B-48; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007328:Insulin; D008055:Lipids; D008074:Lipoproteins; D009570:Nitriles; D011759:Pyrrolidines; D014280:Triglycerides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000077597:Vildagliptin; D000218:Adamantane