TY - JOUR
T1 - Pharmacodynamics of vildagliptin in patients with type 2 diabetes during OGTT.
AU - He, Yan-Ling
AU - Wang, Yibin
AU - Bullock, Julie M
AU - Deacon, Carolyn F
AU - Holst, Jens Juul
AU - Dunning, Beth E
AU - Ligueros-Saylan, Monica
AU - Foley, James E
N1 - Keywords: Adamantane; Adenosine Deaminase; Antigens, CD26; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Glycoproteins; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Nitriles; Pyrrolidines
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
U2 - 10.1177/0091270006299137
DO - 10.1177/0091270006299137
M3 - Journal article
C2 - 17442688
SN - 0091-2700
VL - 47
SP - 633
EP - 641
JO - Journal of Clinical Pharmacology
JF - Journal of Clinical Pharmacology
IS - 5
ER -