Pharmacodynamics of vildagliptin in patients with type 2 diabetes during OGTT.
This randomized, open-label, placebo-controlled, 7-period crossover study assessed dose-response relationships following single oral doses (10-400 mg) of vildagliptin in 16 patients with type 2 diabetes mellitus. Plasma levels of parent drug, dipeptidyl peptidase-4 activity, glucose, insulin, and glucagon were measured during 75-g oral glucose tolerance tests performed after an overnight fast, 30 minutes after drug administration. The t(max) for parent drug was observed between 0.5 and 1.5 hours postdose. Both C(max) and AUC(0-8 h) increased dose proportionately. Both onset and duration of dipeptidyl peptidase-4 inhibition were dose dependent, but >90% inhibition occurred within 45 minutes and was maintained for >/=4 hours after each dose. Glucose excursions and glucagon levels during oral glucose tolerance tests were significantly and similarly decreased after each dose of vildagliptin, and insulin levels were significantly and similarly increased after each dose level. Unlike findings during mixed-meal challenges, vildagliptin increases plasma insulin levels during oral glucose tolerance tests in patients with type 2 diabetes mellitus.
He
Yan-Ling
YL
DMSc, Exploratory Development, Novartis Institutes of Biomedical Research Inc, 400 Technology Square, Building 605, Rm 811, Cambridge, MA 02139-3584, USA. yanling.he@novartis.com
Wang
Yibin
Y
Bullock
Julie M
JM
Deacon
Carolyn F
CF
Holst
Jens Juul
JJ
Dunning
Beth E
BE
Ligueros-Saylan
Monica
M
Foley
James E
JE
D000218:Adamantane / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000097:blood; D058892:Adenosine Deaminase Inhibitors; D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4 / Q000097:blood; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D005951:Glucose Tolerance Test; D006023:Glycoproteins / Q000037:antagonists & inhibitors* / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D011759:Pyrrolidines / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077597:Vildagliptin
D058892:Adenosine Deaminase Inhibitors; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006023:Glycoproteins; D007004:Hypoglycemic Agents; D007328:Insulin; D009570:Nitriles; D011759:Pyrrolidines; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase; D000077597:Vildagliptin; D000218:Adamantane