The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients.

Bogdan Balas; Muhammad R Baig; Catherine Watson; Beth E Dunning; Monica Ligueros-Saylan; Yibin Wang; Yan-Ling He; Celia Darland; Jens J Holst; Carolyn F Deacon; Kenneth Cusi; Andrea Mari; James E Foley; Ralph A DeFronzo

doi:10.1210/jc.2006-1882

The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients.

Bogdan Balas, Muhammad R Baig, Catherine Watson, Beth E Dunning, Monica Ligueros-Saylan, Yibin Wang, Yan-Ling He, Celia Darland, Jens J Holst, Carolyn F Deacon, Kenneth Cusi, Andrea Mari, James E Foley, Ralph A DeFronzo

207 Citations (Scopus)

Abstract

AIMS/HYPOTHESIS: Vildagliptin is a selective dipeptidyl peptidase IV inhibitor that augments meal-stimulated levels of biologically active glucagon-like peptide-1. Chronic vildagliptin treatment decreases postprandial glucose levels and reduces hemoglobin A1c in type 2 diabetic patients. However, little is known about the mechanism(s) by which vildagliptin promotes reduction in plasma glucose concentration. METHODS: Sixteen patients with type 2 diabetes (age, 48+/-3 yr; body mass index, 34.4+/-1.7 kg/m2; hemoglobin A1c, 9.0+/-0.3%) participated in a randomized, double-blind, placebo-controlled trial. On separate days patients received 100 mg vildagliptin or placebo at 1730 h followed 30 min later by a meal tolerance test (MTT) performed with double tracer technique (3-(3)H-glucose iv and 1-(14)C-glucose orally). RESULTS: After vildagliptin, suppression of endogenous glucose production (EGP) during 6-h MTT was greater than with placebo (1.02+/-0.06 vs. 0.74+/-0.06 mg.kg-1.min-1; P=0.004), and insulin secretion rate increased by 21% (P=0.003) despite significant reduction in mean plasma glucose (213+/-4 vs. 230+/-4 mg/dl; P=0.006). Consequently, insulin secretion rate (area under the curve) divided by plasma glucose (area under the curve) increased by 29% (P=0.01). Suppression of plasma glucagon during MTT was 5-fold greater with vildagliptin (P<0.02). The decline in EGP was positively correlated (r=0.55; P<0.03) with the decrease in fasting plasma glucose (change=-14 mg/dl). CONCLUSIONS: During MTT, vildagliptin augments insulin secretion and inhibits glucagon release, leading to enhanced suppression of EGP. During the postprandial period, a single dose of vildagliptin reduced plasma glucose levels by enhancing suppression of EGP.

Original language	English
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	92
Issue number	4
Pages (from-to)	1249-55
Number of pages	6
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2006-1882
Publication status	Published - 2007

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10.1210/jc.2006-1882

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Balas, B., Baig, M. R., Watson, C., Dunning, B. E., Ligueros-Saylan, M., Wang, Y., He, Y-L., Darland, C., Holst, J. J., Deacon, C. F., Cusi, K., Mari, A., Foley, J. E., & DeFronzo, R. A. (2007). The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients. Journal of Clinical Endocrinology and Metabolism, 92(4), 1249-55. https://doi.org/10.1210/jc.2006-1882

The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients. / Balas, Bogdan; Baig, Muhammad R; Watson, Catherine et al.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 92, No. 4, 2007, p. 1249-55.

Research output: Contribution to journal › Journal article › Research › peer-review

Balas, B, Baig, MR, Watson, C, Dunning, BE, Ligueros-Saylan, M, Wang, Y, He, Y-L, Darland, C, Holst, JJ , Deacon, CF, Cusi, K, Mari, A, Foley, JE & DeFronzo, RA 2007, 'The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients.', Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 4, pp. 1249-55. https://doi.org/10.1210/jc.2006-1882

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title = "The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients.",

abstract = "AIMS/HYPOTHESIS: Vildagliptin is a selective dipeptidyl peptidase IV inhibitor that augments meal-stimulated levels of biologically active glucagon-like peptide-1. Chronic vildagliptin treatment decreases postprandial glucose levels and reduces hemoglobin A1c in type 2 diabetic patients. However, little is known about the mechanism(s) by which vildagliptin promotes reduction in plasma glucose concentration. METHODS: Sixteen patients with type 2 diabetes (age, 48+/-3 yr; body mass index, 34.4+/-1.7 kg/m2; hemoglobin A1c, 9.0+/-0.3%) participated in a randomized, double-blind, placebo-controlled trial. On separate days patients received 100 mg vildagliptin or placebo at 1730 h followed 30 min later by a meal tolerance test (MTT) performed with double tracer technique (3-(3)H-glucose iv and 1-(14)C-glucose orally). RESULTS: After vildagliptin, suppression of endogenous glucose production (EGP) during 6-h MTT was greater than with placebo (1.02+/-0.06 vs. 0.74+/-0.06 mg.kg-1.min-1; P=0.004), and insulin secretion rate increased by 21% (P=0.003) despite significant reduction in mean plasma glucose (213+/-4 vs. 230+/-4 mg/dl; P=0.006). Consequently, insulin secretion rate (area under the curve) divided by plasma glucose (area under the curve) increased by 29% (P=0.01). Suppression of plasma glucagon during MTT was 5-fold greater with vildagliptin (P<0.02). The decline in EGP was positively correlated (r=0.55; P<0.03) with the decrease in fasting plasma glucose (change=-14 mg/dl). CONCLUSIONS: During MTT, vildagliptin augments insulin secretion and inhibits glucagon release, leading to enhanced suppression of EGP. During the postprandial period, a single dose of vildagliptin reduced plasma glucose levels by enhancing suppression of EGP.",

author = "Bogdan Balas and Baig, {Muhammad R} and Catherine Watson and Dunning, {Beth E} and Monica Ligueros-Saylan and Yibin Wang and Yan-Ling He and Celia Darland and Holst, {Jens J} and Deacon, {Carolyn F} and Kenneth Cusi and Andrea Mari and Foley, {James E} and DeFronzo, {Ralph A}",

note = "Keywords: Adamantane; Adenosine Deaminase; Antigens, CD26; Body Mass Index; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Enzyme Inhibitors; Female; Glucose; Glycoproteins; Hemoglobin A, Glycosylated; Humans; Hypoglycemic Agents; Islets of Langerhans; Kinetics; Male; Middle Aged; Nitriles; Obesity; Pyrrolidines",

year = "2007",

doi = "10.1210/jc.2006-1882",

language = "English",

volume = "92",

pages = "1249--55",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

number = "4",

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TY - JOUR

T1 - The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients.

AU - Balas, Bogdan

AU - Baig, Muhammad R

AU - Watson, Catherine

AU - Dunning, Beth E

AU - Ligueros-Saylan, Monica

AU - Wang, Yibin

AU - He, Yan-Ling

AU - Darland, Celia

AU - Holst, Jens J

AU - Deacon, Carolyn F

AU - Cusi, Kenneth

AU - Mari, Andrea

AU - Foley, James E

AU - DeFronzo, Ralph A

N1 - Keywords: Adamantane; Adenosine Deaminase; Antigens, CD26; Body Mass Index; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Enzyme Inhibitors; Female; Glucose; Glycoproteins; Hemoglobin A, Glycosylated; Humans; Hypoglycemic Agents; Islets of Langerhans; Kinetics; Male; Middle Aged; Nitriles; Obesity; Pyrrolidines

PY - 2007

Y1 - 2007

N2 - AIMS/HYPOTHESIS: Vildagliptin is a selective dipeptidyl peptidase IV inhibitor that augments meal-stimulated levels of biologically active glucagon-like peptide-1. Chronic vildagliptin treatment decreases postprandial glucose levels and reduces hemoglobin A1c in type 2 diabetic patients. However, little is known about the mechanism(s) by which vildagliptin promotes reduction in plasma glucose concentration. METHODS: Sixteen patients with type 2 diabetes (age, 48+/-3 yr; body mass index, 34.4+/-1.7 kg/m2; hemoglobin A1c, 9.0+/-0.3%) participated in a randomized, double-blind, placebo-controlled trial. On separate days patients received 100 mg vildagliptin or placebo at 1730 h followed 30 min later by a meal tolerance test (MTT) performed with double tracer technique (3-(3)H-glucose iv and 1-(14)C-glucose orally). RESULTS: After vildagliptin, suppression of endogenous glucose production (EGP) during 6-h MTT was greater than with placebo (1.02+/-0.06 vs. 0.74+/-0.06 mg.kg-1.min-1; P=0.004), and insulin secretion rate increased by 21% (P=0.003) despite significant reduction in mean plasma glucose (213+/-4 vs. 230+/-4 mg/dl; P=0.006). Consequently, insulin secretion rate (area under the curve) divided by plasma glucose (area under the curve) increased by 29% (P=0.01). Suppression of plasma glucagon during MTT was 5-fold greater with vildagliptin (P<0.02). The decline in EGP was positively correlated (r=0.55; P<0.03) with the decrease in fasting plasma glucose (change=-14 mg/dl). CONCLUSIONS: During MTT, vildagliptin augments insulin secretion and inhibits glucagon release, leading to enhanced suppression of EGP. During the postprandial period, a single dose of vildagliptin reduced plasma glucose levels by enhancing suppression of EGP.

AB - AIMS/HYPOTHESIS: Vildagliptin is a selective dipeptidyl peptidase IV inhibitor that augments meal-stimulated levels of biologically active glucagon-like peptide-1. Chronic vildagliptin treatment decreases postprandial glucose levels and reduces hemoglobin A1c in type 2 diabetic patients. However, little is known about the mechanism(s) by which vildagliptin promotes reduction in plasma glucose concentration. METHODS: Sixteen patients with type 2 diabetes (age, 48+/-3 yr; body mass index, 34.4+/-1.7 kg/m2; hemoglobin A1c, 9.0+/-0.3%) participated in a randomized, double-blind, placebo-controlled trial. On separate days patients received 100 mg vildagliptin or placebo at 1730 h followed 30 min later by a meal tolerance test (MTT) performed with double tracer technique (3-(3)H-glucose iv and 1-(14)C-glucose orally). RESULTS: After vildagliptin, suppression of endogenous glucose production (EGP) during 6-h MTT was greater than with placebo (1.02+/-0.06 vs. 0.74+/-0.06 mg.kg-1.min-1; P=0.004), and insulin secretion rate increased by 21% (P=0.003) despite significant reduction in mean plasma glucose (213+/-4 vs. 230+/-4 mg/dl; P=0.006). Consequently, insulin secretion rate (area under the curve) divided by plasma glucose (area under the curve) increased by 29% (P=0.01). Suppression of plasma glucagon during MTT was 5-fold greater with vildagliptin (P<0.02). The decline in EGP was positively correlated (r=0.55; P<0.03) with the decrease in fasting plasma glucose (change=-14 mg/dl). CONCLUSIONS: During MTT, vildagliptin augments insulin secretion and inhibits glucagon release, leading to enhanced suppression of EGP. During the postprandial period, a single dose of vildagliptin reduced plasma glucose levels by enhancing suppression of EGP.

U2 - 10.1210/jc.2006-1882

DO - 10.1210/jc.2006-1882

M3 - Journal article

C2 - 17244786

SN - 0021-972X

VL - 92

SP - 1249

EP - 1255

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 4

ER -

The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients.

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