Effects of the dipeptidyl peptidase-IV inhibitor vildagliptin on incretin hormones, islet function, and postprandial glycemia in subjects with impaired glucose tolerance.

Julio Rosenstock; James E Foley; Marc Rendell; Mona Landin-Olsson; Jens J Holst; Carolyn F Deacon; Erika Rochotte; Michelle A Baron

doi:10.2337/dc07-1616

Effects of the dipeptidyl peptidase-IV inhibitor vildagliptin on incretin hormones, islet function, and postprandial glycemia in subjects with impaired glucose tolerance.

Julio Rosenstock, James E Foley, Marc Rendell, Mona Landin-Olsson, Jens J Holst, Carolyn F Deacon, Erika Rochotte, Michelle A Baron

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

134 Citationer (Scopus)

Abstract

Udgivelsesdato: 2008-Jan

Originalsprog	Engelsk
Tidsskrift	Diabetes Care
Vol/bind	31
Udgave nummer	1
Sider (fra-til)	30-5
Antal sider	5
ISSN	0149-5992
DOI	https://doi.org/10.2337/dc07-1616
Status	Udgivet - 2008

Bibliografisk note

Keywords: Adamantane; Blood Glucose; C-Peptide; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose Intolerance; Humans; Inulin; Kinetics; Male; Nitriles; Placebos; Postprandial Period; Pyrrolidines

Adgang til dokumentet

10.2337/dc07-1616

Citationsformater

@article{4da51650ab4911ddb5e9000ea68e967b,

title = "Effects of the dipeptidyl peptidase-IV inhibitor vildagliptin on incretin hormones, islet function, and postprandial glycemia in subjects with impaired glucose tolerance.",

abstract = "OBJECTIVE: This study was conducted to determine the effects of vildagliptin on incretin hormone levels, islet function, and postprandial glucose control in subjects with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A 12-week, double-blind, randomized, parallel-group study comparing vildagliptin (50 mg q.d.) and placebo was conducted in 179 subjects with IGT (2-h glucose 9.1 mmol/l, A1C 5.9%). Plasma levels of intact glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP), glucose, insulin, C-peptide, and glucagon were measured during standard meal tests performed at baseline and at week 12. Insulin secretory rate (ISR) was estimated by C-peptide deconvolution. The between-group differences (vildagliptin - placebo) in the adjusted mean changes from baseline to end point in the total and incremental (Delta) area under the curve (AUC)(0-2 h) for these analytes were assessed by ANCOVA; glucose AUC(0-2 h) was the primary outcome variable. RESULTS: Relative to placebo, vildagliptin increased GLP-1 (DeltaAUC, +6.0 +/- 1.2 pmol x l(-1) x h(-1), P < 0.001) and GIP (DeltaAUC, +46.8 +/- 5.4 pmol . l(-1) x h(-1), P < 0.001) and decreased glucagon (DeltaAUC, -3.0 +/- 1.0 pmol x l(-1) x h(-1), P = 0.003). Although postprandial insulin levels were unaffected (DeltaAUC, +20.8 +/- 35.7 pmol x l(-1) x h(-1), P = 0.561), prandial glucose excursions were reduced (DeltaAUC, -1.0 +/- 0.3 mmol x l(-1) x h(-1), P < 0.001), representing an approximately 30% decrease relative to placebo. Beta-cell function as assessed by the ISR AUC(0-2 h)/glucose AUC(0-2 h) was significantly increased (+6.4 +/- 2.0 pmol x min(-1) x m(-2) x mmol x l(-1), P = 0.002). Adverse event profiles were similar in the two treatment groups, and no hypoglycemia was reported. CONCLUSIONS: The known effects of vildagliptin on incretin levels and islet function in type 2 diabetes were reproduced in subjects with IGT, with a 32% reduction in postprandial glucose excursions and no evidence of hypoglycemia or weight gain.",

author = "Julio Rosenstock and Foley, {James E} and Marc Rendell and Mona Landin-Olsson and Holst, {Jens J} and Deacon, {Carolyn F} and Erika Rochotte and Baron, {Michelle A}",

note = "Keywords: Adamantane; Blood Glucose; C-Peptide; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose Intolerance; Humans; Inulin; Kinetics; Male; Nitriles; Placebos; Postprandial Period; Pyrrolidines",

year = "2008",

doi = "10.2337/dc07-1616",

language = "English",

volume = "31",

pages = "30--5",

journal = "Diabetes Care",

issn = "0149-5992",

publisher = "American Diabetes Association",

number = "1",

}

TY - JOUR

T1 - Effects of the dipeptidyl peptidase-IV inhibitor vildagliptin on incretin hormones, islet function, and postprandial glycemia in subjects with impaired glucose tolerance.

AU - Rosenstock, Julio

AU - Foley, James E

AU - Rendell, Marc

AU - Landin-Olsson, Mona

AU - Holst, Jens J

AU - Deacon, Carolyn F

AU - Rochotte, Erika

AU - Baron, Michelle A

N1 - Keywords: Adamantane; Blood Glucose; C-Peptide; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose Intolerance; Humans; Inulin; Kinetics; Male; Nitriles; Placebos; Postprandial Period; Pyrrolidines

PY - 2008

Y1 - 2008

N2 - OBJECTIVE: This study was conducted to determine the effects of vildagliptin on incretin hormone levels, islet function, and postprandial glucose control in subjects with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A 12-week, double-blind, randomized, parallel-group study comparing vildagliptin (50 mg q.d.) and placebo was conducted in 179 subjects with IGT (2-h glucose 9.1 mmol/l, A1C 5.9%). Plasma levels of intact glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP), glucose, insulin, C-peptide, and glucagon were measured during standard meal tests performed at baseline and at week 12. Insulin secretory rate (ISR) was estimated by C-peptide deconvolution. The between-group differences (vildagliptin - placebo) in the adjusted mean changes from baseline to end point in the total and incremental (Delta) area under the curve (AUC)(0-2 h) for these analytes were assessed by ANCOVA; glucose AUC(0-2 h) was the primary outcome variable. RESULTS: Relative to placebo, vildagliptin increased GLP-1 (DeltaAUC, +6.0 +/- 1.2 pmol x l(-1) x h(-1), P < 0.001) and GIP (DeltaAUC, +46.8 +/- 5.4 pmol . l(-1) x h(-1), P < 0.001) and decreased glucagon (DeltaAUC, -3.0 +/- 1.0 pmol x l(-1) x h(-1), P = 0.003). Although postprandial insulin levels were unaffected (DeltaAUC, +20.8 +/- 35.7 pmol x l(-1) x h(-1), P = 0.561), prandial glucose excursions were reduced (DeltaAUC, -1.0 +/- 0.3 mmol x l(-1) x h(-1), P < 0.001), representing an approximately 30% decrease relative to placebo. Beta-cell function as assessed by the ISR AUC(0-2 h)/glucose AUC(0-2 h) was significantly increased (+6.4 +/- 2.0 pmol x min(-1) x m(-2) x mmol x l(-1), P = 0.002). Adverse event profiles were similar in the two treatment groups, and no hypoglycemia was reported. CONCLUSIONS: The known effects of vildagliptin on incretin levels and islet function in type 2 diabetes were reproduced in subjects with IGT, with a 32% reduction in postprandial glucose excursions and no evidence of hypoglycemia or weight gain.

AB - OBJECTIVE: This study was conducted to determine the effects of vildagliptin on incretin hormone levels, islet function, and postprandial glucose control in subjects with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A 12-week, double-blind, randomized, parallel-group study comparing vildagliptin (50 mg q.d.) and placebo was conducted in 179 subjects with IGT (2-h glucose 9.1 mmol/l, A1C 5.9%). Plasma levels of intact glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP), glucose, insulin, C-peptide, and glucagon were measured during standard meal tests performed at baseline and at week 12. Insulin secretory rate (ISR) was estimated by C-peptide deconvolution. The between-group differences (vildagliptin - placebo) in the adjusted mean changes from baseline to end point in the total and incremental (Delta) area under the curve (AUC)(0-2 h) for these analytes were assessed by ANCOVA; glucose AUC(0-2 h) was the primary outcome variable. RESULTS: Relative to placebo, vildagliptin increased GLP-1 (DeltaAUC, +6.0 +/- 1.2 pmol x l(-1) x h(-1), P < 0.001) and GIP (DeltaAUC, +46.8 +/- 5.4 pmol . l(-1) x h(-1), P < 0.001) and decreased glucagon (DeltaAUC, -3.0 +/- 1.0 pmol x l(-1) x h(-1), P = 0.003). Although postprandial insulin levels were unaffected (DeltaAUC, +20.8 +/- 35.7 pmol x l(-1) x h(-1), P = 0.561), prandial glucose excursions were reduced (DeltaAUC, -1.0 +/- 0.3 mmol x l(-1) x h(-1), P < 0.001), representing an approximately 30% decrease relative to placebo. Beta-cell function as assessed by the ISR AUC(0-2 h)/glucose AUC(0-2 h) was significantly increased (+6.4 +/- 2.0 pmol x min(-1) x m(-2) x mmol x l(-1), P = 0.002). Adverse event profiles were similar in the two treatment groups, and no hypoglycemia was reported. CONCLUSIONS: The known effects of vildagliptin on incretin levels and islet function in type 2 diabetes were reproduced in subjects with IGT, with a 32% reduction in postprandial glucose excursions and no evidence of hypoglycemia or weight gain.

U2 - 10.2337/dc07-1616

DO - 10.2337/dc07-1616

M3 - Journal article

C2 - 17947341

SN - 0149-5992

VL - 31

SP - 30

EP - 35

JO - Diabetes Care

JF - Diabetes Care

IS - 1

ER -