Effects of dipeptidyl peptidase-4 inhibition on gastrointestinal function, meal appearance, and glucose metabolism in type 2 diabetes

Adrian Vella, Gerlies Bock, Paula D. Giesler, Duane B. Burton, Denise B. Serra, Monica Ligueros Saylan, Beth E. Dunning, James E. Foley, Robert A. Rizza, Michael Camilleri

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE - We sought to determine whether alterations in meal absorption and gastric emptying contribute to the mechanism by which inhibitors of dipeptidyl peptidase-4 (DPP-4) lower postprandial glucose concentrations. RESEARCH DESIGN AND METHODS - We simultaneously measured gastric emptying, meal appearance, endogenous glucose production, and glucose disappearance in 14 subjects with type 2 diabetes treated with either vildaglipitin (50 mg b.i.d.) or placebo for 10 days using a double-blind, placebo-controlled, randomized, crossover design. RESULTS - Fasting (7.3 ± 0.5 vs. 7.9 ± 0.5 mmol/l) and peak postprandial (14.1 ± 0.6 vs. 15.9 ± 0.9 mmol/l) glucose concentrations were lower (P < 0.01) after vildagliptin treatment than placebo. Despite lower glucose concentrations, postprandial insulin and C-peptide concentrations did not differ during the two treatments. On the other hand, the integrated (area under the curve) postprandial glucagon concentrations were lower (20.9 ± 1.6 vs. 23.7 ± 1.3 mg/ml per 5 h, P < 0.05), and glucagon-like peptide 1 (GLP-1) concentrations were higher (1,878 ± 270 vs. 1,277 ± 312 pmol/l per 5 h, P = 0.001) during vildagliptin administration compared with placebo. Gastric emptying and meal appearance did not differ between treatments. CONCLUSIONS - Vildagliptin does not alter gastric emptying or the rate of entry of ingested glucose into the systemic circulation in humans. DPP-4 inhibitors do not lower postprandial glucose concentrations by altering the rate of nutrient absorption or delivery to systemic circulation. Alterations in islet function, secondary to increased circulating concentrations of active GLP-1, are associated with the decreased postprandial glycemic excursion observed in the presence of vildagliptin.

Original languageEnglish (US)
Pages (from-to)1475-1480
Number of pages6
JournalDiabetes
Volume56
Issue number5
DOIs
StatePublished - May 2007

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Dipeptidyl Peptidase 4
Type 2 Diabetes Mellitus
Meals
Gastric Emptying
Glucose
Placebos
Dipeptidyl-Peptidase IV Inhibitors
Glucagon-Like Peptide 1
C-Peptide
Inhibition (Psychology)
Glucagon
Cross-Over Studies
Area Under Curve
Fasting
Research Design
Therapeutics
Insulin
Food
vildagliptin

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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Effects of dipeptidyl peptidase-4 inhibition on gastrointestinal function, meal appearance, and glucose metabolism in type 2 diabetes. / Vella, Adrian; Bock, Gerlies; Giesler, Paula D.; Burton, Duane B.; Serra, Denise B.; Saylan, Monica Ligueros; Dunning, Beth E.; Foley, James E.; Rizza, Robert A.; Camilleri, Michael.

In: Diabetes, Vol. 56, No. 5, 05.2007, p. 1475-1480.

Research output: Contribution to journalArticle

Vella, A, Bock, G, Giesler, PD, Burton, DB, Serra, DB, Saylan, ML, Dunning, BE, Foley, JE, Rizza, RA & Camilleri, M 2007, 'Effects of dipeptidyl peptidase-4 inhibition on gastrointestinal function, meal appearance, and glucose metabolism in type 2 diabetes', Diabetes, vol. 56, no. 5, pp. 1475-1480. https://doi.org/10.2337/db07-0136
Vella, Adrian ; Bock, Gerlies ; Giesler, Paula D. ; Burton, Duane B. ; Serra, Denise B. ; Saylan, Monica Ligueros ; Dunning, Beth E. ; Foley, James E. ; Rizza, Robert A. ; Camilleri, Michael. / Effects of dipeptidyl peptidase-4 inhibition on gastrointestinal function, meal appearance, and glucose metabolism in type 2 diabetes. In: Diabetes. 2007 ; Vol. 56, No. 5. pp. 1475-1480.
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abstract = "OBJECTIVE - We sought to determine whether alterations in meal absorption and gastric emptying contribute to the mechanism by which inhibitors of dipeptidyl peptidase-4 (DPP-4) lower postprandial glucose concentrations. RESEARCH DESIGN AND METHODS - We simultaneously measured gastric emptying, meal appearance, endogenous glucose production, and glucose disappearance in 14 subjects with type 2 diabetes treated with either vildaglipitin (50 mg b.i.d.) or placebo for 10 days using a double-blind, placebo-controlled, randomized, crossover design. RESULTS - Fasting (7.3 ± 0.5 vs. 7.9 ± 0.5 mmol/l) and peak postprandial (14.1 ± 0.6 vs. 15.9 ± 0.9 mmol/l) glucose concentrations were lower (P < 0.01) after vildagliptin treatment than placebo. Despite lower glucose concentrations, postprandial insulin and C-peptide concentrations did not differ during the two treatments. On the other hand, the integrated (area under the curve) postprandial glucagon concentrations were lower (20.9 ± 1.6 vs. 23.7 ± 1.3 mg/ml per 5 h, P < 0.05), and glucagon-like peptide 1 (GLP-1) concentrations were higher (1,878 ± 270 vs. 1,277 ± 312 pmol/l per 5 h, P = 0.001) during vildagliptin administration compared with placebo. Gastric emptying and meal appearance did not differ between treatments. CONCLUSIONS - Vildagliptin does not alter gastric emptying or the rate of entry of ingested glucose into the systemic circulation in humans. DPP-4 inhibitors do not lower postprandial glucose concentrations by altering the rate of nutrient absorption or delivery to systemic circulation. Alterations in islet function, secondary to increased circulating concentrations of active GLP-1, are associated with the decreased postprandial glycemic excursion observed in the presence of vildagliptin.",
author = "Adrian Vella and Gerlies Bock and Giesler, {Paula D.} and Burton, {Duane B.} and Serra, {Denise B.} and Saylan, {Monica Ligueros} and Dunning, {Beth E.} and Foley, {James E.} and Rizza, {Robert A.} and Michael Camilleri",
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T1 - Effects of dipeptidyl peptidase-4 inhibition on gastrointestinal function, meal appearance, and glucose metabolism in type 2 diabetes

AU - Vella, Adrian

AU - Bock, Gerlies

AU - Giesler, Paula D.

AU - Burton, Duane B.

AU - Serra, Denise B.

AU - Saylan, Monica Ligueros

AU - Dunning, Beth E.

AU - Foley, James E.

AU - Rizza, Robert A.

AU - Camilleri, Michael

PY - 2007/5

Y1 - 2007/5

N2 - OBJECTIVE - We sought to determine whether alterations in meal absorption and gastric emptying contribute to the mechanism by which inhibitors of dipeptidyl peptidase-4 (DPP-4) lower postprandial glucose concentrations. RESEARCH DESIGN AND METHODS - We simultaneously measured gastric emptying, meal appearance, endogenous glucose production, and glucose disappearance in 14 subjects with type 2 diabetes treated with either vildaglipitin (50 mg b.i.d.) or placebo for 10 days using a double-blind, placebo-controlled, randomized, crossover design. RESULTS - Fasting (7.3 ± 0.5 vs. 7.9 ± 0.5 mmol/l) and peak postprandial (14.1 ± 0.6 vs. 15.9 ± 0.9 mmol/l) glucose concentrations were lower (P < 0.01) after vildagliptin treatment than placebo. Despite lower glucose concentrations, postprandial insulin and C-peptide concentrations did not differ during the two treatments. On the other hand, the integrated (area under the curve) postprandial glucagon concentrations were lower (20.9 ± 1.6 vs. 23.7 ± 1.3 mg/ml per 5 h, P < 0.05), and glucagon-like peptide 1 (GLP-1) concentrations were higher (1,878 ± 270 vs. 1,277 ± 312 pmol/l per 5 h, P = 0.001) during vildagliptin administration compared with placebo. Gastric emptying and meal appearance did not differ between treatments. CONCLUSIONS - Vildagliptin does not alter gastric emptying or the rate of entry of ingested glucose into the systemic circulation in humans. DPP-4 inhibitors do not lower postprandial glucose concentrations by altering the rate of nutrient absorption or delivery to systemic circulation. Alterations in islet function, secondary to increased circulating concentrations of active GLP-1, are associated with the decreased postprandial glycemic excursion observed in the presence of vildagliptin.

AB - OBJECTIVE - We sought to determine whether alterations in meal absorption and gastric emptying contribute to the mechanism by which inhibitors of dipeptidyl peptidase-4 (DPP-4) lower postprandial glucose concentrations. RESEARCH DESIGN AND METHODS - We simultaneously measured gastric emptying, meal appearance, endogenous glucose production, and glucose disappearance in 14 subjects with type 2 diabetes treated with either vildaglipitin (50 mg b.i.d.) or placebo for 10 days using a double-blind, placebo-controlled, randomized, crossover design. RESULTS - Fasting (7.3 ± 0.5 vs. 7.9 ± 0.5 mmol/l) and peak postprandial (14.1 ± 0.6 vs. 15.9 ± 0.9 mmol/l) glucose concentrations were lower (P < 0.01) after vildagliptin treatment than placebo. Despite lower glucose concentrations, postprandial insulin and C-peptide concentrations did not differ during the two treatments. On the other hand, the integrated (area under the curve) postprandial glucagon concentrations were lower (20.9 ± 1.6 vs. 23.7 ± 1.3 mg/ml per 5 h, P < 0.05), and glucagon-like peptide 1 (GLP-1) concentrations were higher (1,878 ± 270 vs. 1,277 ± 312 pmol/l per 5 h, P = 0.001) during vildagliptin administration compared with placebo. Gastric emptying and meal appearance did not differ between treatments. CONCLUSIONS - Vildagliptin does not alter gastric emptying or the rate of entry of ingested glucose into the systemic circulation in humans. DPP-4 inhibitors do not lower postprandial glucose concentrations by altering the rate of nutrient absorption or delivery to systemic circulation. Alterations in islet function, secondary to increased circulating concentrations of active GLP-1, are associated with the decreased postprandial glycemic excursion observed in the presence of vildagliptin.

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