Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Clinical Endocrinology and Metabolism |
| Vol/bind | 91 |
| Udgave nummer | 11 |
| Sider (fra-til) | 4612-9 |
| Antal sider | 7 |
| ISSN | 0021-972X |
| DOI | |
| Status | Udgivet - 2006 |
Bibliografisk note
Keywords: Administration, Oral; Adult; Antigens, CD26; Area Under Curve; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Enzyme Inhibitors; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Male; Middle Aged; Placebos; Pyrazines; TriazolesAdgang til dokumentet
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Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes. / Herman, Gary A; Bergman, Arthur; Stevens, Catherine; Kotey, Paul; Yi, Bingming; Zhao, Peng; Dietrich, Bruno; Golor, George; Schrodter, Andreas; Keymeulen, Bart; Lasseter, Kenneth C; Kipnes, Mark S; Snyder, Karen; Hilliard, Deborah; Tanen, Michael; Cilissen, Caroline; De Smet, Marina; de Lepeleire, Inge; Van Dyck, Kristien; Wang, Amy Q; Zeng, Wei; Davies, Michael J; Tanaka, Wesley; Holst, Jens J; Deacon, Carolyn F; Gottesdiener, Keith M; Wagner, John A.
I: Journal of Clinical Endocrinology and Metabolism, Bind 91, Nr. 11, 2006, s. 4612-9.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes.
AU - Herman, Gary A
AU - Bergman, Arthur
AU - Stevens, Catherine
AU - Kotey, Paul
AU - Yi, Bingming
AU - Zhao, Peng
AU - Dietrich, Bruno
AU - Golor, George
AU - Schrodter, Andreas
AU - Keymeulen, Bart
AU - Lasseter, Kenneth C
AU - Kipnes, Mark S
AU - Snyder, Karen
AU - Hilliard, Deborah
AU - Tanen, Michael
AU - Cilissen, Caroline
AU - De Smet, Marina
AU - de Lepeleire, Inge
AU - Van Dyck, Kristien
AU - Wang, Amy Q
AU - Zeng, Wei
AU - Davies, Michael J
AU - Tanaka, Wesley
AU - Holst, Jens J
AU - Deacon, Carolyn F
AU - Gottesdiener, Keith M
AU - Wagner, John A
N1 - Keywords: Administration, Oral; Adult; Antigens, CD26; Area Under Curve; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Enzyme Inhibitors; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Male; Middle Aged; Placebos; Pyrazines; Triazoles
PY - 2006
Y1 - 2006
N2 - CONTEXT: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral antihyperglycemic agents in development for the treatment of type 2 diabetes. The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test (OGTT) were evaluated. OBJECTIVE: The objective of the study was to examine the pharmacodynamics, pharmacokinetics, and tolerability of sitagliptin. DESIGN: This was a randomized, double-blind, placebo-controlled, three-period, single-dose crossover study. SETTING: The study was conducted at six investigational sites. PATIENTS: The study population consisted of 58 patients with type 2 diabetes who were not on antihyperglycemic agents. INTERVENTIONS: Interventions included sitagliptin 25 mg, sitagliptin 200 mg, or placebo. MAIN OUTCOME MEASURES: Measurements included plasma DPP-4 activity; post-OGTT glucose excursion; active and total incretin GIP levels; insulin, C-peptide, and glucagon concentrations; and sitagliptin pharmacokinetics. RESULTS: Sitagliptin dose-dependently inhibited plasma DPP-4 activity over 24 h, enhanced active GLP-1 and GIP levels, increased insulin/C-peptide, decreased glucagon, and reduced glycemic excursion after OGTTs administered at 2 and 24 h after single oral 25- or 200-mg doses of sitagliptin. Sitagliptin was generally well tolerated, with no hypoglycemic events. CONCLUSIONS: In this study in patients with type 2 diabetes, near maximal glucose-lowering efficacy of sitagliptin after single oral doses was associated with inhibition of plasma DPP-4 activity of 80% or greater, corresponding to a plasma sitagliptin concentration of 100 nm or greater, and an augmentation of active GLP-1 and GIP levels of 2-fold or higher after an OGTT.
AB - CONTEXT: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral antihyperglycemic agents in development for the treatment of type 2 diabetes. The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test (OGTT) were evaluated. OBJECTIVE: The objective of the study was to examine the pharmacodynamics, pharmacokinetics, and tolerability of sitagliptin. DESIGN: This was a randomized, double-blind, placebo-controlled, three-period, single-dose crossover study. SETTING: The study was conducted at six investigational sites. PATIENTS: The study population consisted of 58 patients with type 2 diabetes who were not on antihyperglycemic agents. INTERVENTIONS: Interventions included sitagliptin 25 mg, sitagliptin 200 mg, or placebo. MAIN OUTCOME MEASURES: Measurements included plasma DPP-4 activity; post-OGTT glucose excursion; active and total incretin GIP levels; insulin, C-peptide, and glucagon concentrations; and sitagliptin pharmacokinetics. RESULTS: Sitagliptin dose-dependently inhibited plasma DPP-4 activity over 24 h, enhanced active GLP-1 and GIP levels, increased insulin/C-peptide, decreased glucagon, and reduced glycemic excursion after OGTTs administered at 2 and 24 h after single oral 25- or 200-mg doses of sitagliptin. Sitagliptin was generally well tolerated, with no hypoglycemic events. CONCLUSIONS: In this study in patients with type 2 diabetes, near maximal glucose-lowering efficacy of sitagliptin after single oral doses was associated with inhibition of plasma DPP-4 activity of 80% or greater, corresponding to a plasma sitagliptin concentration of 100 nm or greater, and an augmentation of active GLP-1 and GIP levels of 2-fold or higher after an OGTT.
U2 - 10.1210/jc.2006-1009
DO - 10.1210/jc.2006-1009
M3 - Journal article
C2 - 16912128
VL - 91
SP - 4612
EP - 4619
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 11
ER -