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.

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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.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 91, No. 11, 2006, p. 4612-9.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Herman, GA, Bergman, A, Stevens, C, Kotey, P, Yi, B, Zhao, P, Dietrich, B, Golor, G, Schrodter, A, Keymeulen, B, Lasseter, KC, Kipnes, MS, Snyder, K, Hilliard, D, Tanen, M, Cilissen, C, De Smet, M, de Lepeleire, I, Van Dyck, K, Wang, AQ, Zeng, W, Davies, MJ, Tanaka, W, Holst, JJ, Deacon, CF, Gottesdiener, KM & Wagner, JA 2006, '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.', Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 11, pp. 4612-9. https://doi.org/10.1210/jc.2006-1009

APA

Herman, G. A., Bergman, A., Stevens, C., Kotey, P., Yi, B., Zhao, P., ... Wagner, J. A. (2006). 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. Journal of Clinical Endocrinology and Metabolism, 91(11), 4612-9. https://doi.org/10.1210/jc.2006-1009

Vancouver

Herman GA, Bergman A, Stevens C, Kotey P, Yi B, Zhao P et al. 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. Journal of Clinical Endocrinology and Metabolism. 2006;91(11):4612-9. https://doi.org/10.1210/jc.2006-1009

Author

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. / 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. In: Journal of Clinical Endocrinology and Metabolism. 2006 ; Vol. 91, No. 11. pp. 4612-9.

Bibtex

@article{72de4890ab4b11ddb5e9000ea68e967b,
title = "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.",
abstract = "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.",
author = "Herman, {Gary A} and Arthur Bergman and Catherine Stevens and Paul Kotey and Bingming Yi and Peng Zhao and Bruno Dietrich and George Golor and Andreas Schrodter and Bart Keymeulen and Lasseter, {Kenneth C} and Kipnes, {Mark S} and Karen Snyder and Deborah Hilliard and Michael Tanen and Caroline Cilissen and {De Smet}, Marina and {de Lepeleire}, Inge and {Van Dyck}, Kristien and Wang, {Amy Q} and Wei Zeng and Davies, {Michael J} and Wesley Tanaka and Holst, {Jens J} and Deacon, {Carolyn F} and Gottesdiener, {Keith M} and Wagner, {John A}",
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; Triazoles",
year = "2006",
doi = "10.1210/jc.2006-1009",
language = "English",
volume = "91",
pages = "4612--9",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Oxford University Press",
number = "11",

}

RIS

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 -

ID: 8417107