Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1

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Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1. / Migoya, E M; Bergeron, R; Miller, J L; Snyder, R N K; Tanen, M; Hilliard, D; Weiss, B; Larson, P; Gutierrez, M; Jiang, G; Liu, F.; Pryor, K A; Yao, J; Zhu, L; Holst, Jens Juul; Deacon, C; Herman, G; Thornberry, N; Amatruda, J; Williams-Herman, D; Wagner, J A; SinhaRoy, R.

In: Clinical Pharmacology and Therapeutics, Vol. 88, No. 6, 01.12.2010, p. 801-8.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Migoya, EM, Bergeron, R, Miller, JL, Snyder, RNK, Tanen, M, Hilliard, D, Weiss, B, Larson, P, Gutierrez, M, Jiang, G, Liu, F, Pryor, KA, Yao, J, Zhu, L, Holst, JJ, Deacon, C, Herman, G, Thornberry, N, Amatruda, J, Williams-Herman, D, Wagner, JA & SinhaRoy, R 2010, 'Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1', Clinical Pharmacology and Therapeutics, vol. 88, no. 6, pp. 801-8. https://doi.org/10.1038/clpt.2010.184

APA

Migoya, E. M., Bergeron, R., Miller, J. L., Snyder, R. N. K., Tanen, M., Hilliard, D., ... SinhaRoy, R. (2010). Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1. Clinical Pharmacology and Therapeutics, 88(6), 801-8. https://doi.org/10.1038/clpt.2010.184

Vancouver

Migoya EM, Bergeron R, Miller JL, Snyder RNK, Tanen M, Hilliard D et al. Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1. Clinical Pharmacology and Therapeutics. 2010 Dec 1;88(6):801-8. https://doi.org/10.1038/clpt.2010.184

Author

Migoya, E M ; Bergeron, R ; Miller, J L ; Snyder, R N K ; Tanen, M ; Hilliard, D ; Weiss, B ; Larson, P ; Gutierrez, M ; Jiang, G ; Liu, F. ; Pryor, K A ; Yao, J ; Zhu, L ; Holst, Jens Juul ; Deacon, C ; Herman, G ; Thornberry, N ; Amatruda, J ; Williams-Herman, D ; Wagner, J A ; SinhaRoy, R. / Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1. In: Clinical Pharmacology and Therapeutics. 2010 ; Vol. 88, No. 6. pp. 801-8.

Bibtex

@article{9b20fc0d720c4ba48fa886dc24f20c1c,
title = "Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1",
abstract = "The aim of the study was to investigate the effects of a dipeptidyl peptidase-4 (DPP-4) inhibitor, of metformin, and of the combination of the two agents, on incretin hormone concentrations. Active and inactive (or total) incretin plasma concentrations, plasma DPP-4 activity, and preproglucagon (GCG) gene expression were determined after administration of each agent alone or in combination to mice with diet-induced obesity (DIO) and to healthy human subjects. In mice, metformin increased Gcg expression in the large intestine and elevated the plasma concentrations of inactive glucagon-like peptide 1 (GLP-1) (9-36) and glucagon. In healthy subjects, a DPP-4 inhibitor elevated both active GLP-1 and glucose dependent insulinotropic polypeptide (GIP), metformin increased total GLP-1 (but not GIP), and the combination resulted in additive increases in active GLP-1 plasma concentrations. Metformin did not inhibit plasma DPP-4 activity either in vitro or in vivo. The study results show that metformin is not a DPP-4 inhibitor but rather enhances precursor GCG expression in the large intestine, resulting in increased total GLP-1 concentrations. DPP-4 inhibitors and metformin have complementary mechanisms of action and additive effects with respect to increasing the concentrations of active GLP-1 in plasma.",
keywords = "Adolescent, Adult, Animals, Cross-Over Studies, Dipeptidyl-Peptidase IV Inhibitors, Double-Blind Method, Drug Therapy, Combination, Female, Glucagon-Like Peptide 1, Humans, Male, Metformin, Mice, Mice, Inbred C57BL, Middle Aged, Obesity, Young Adult",
author = "Migoya, {E M} and R Bergeron and Miller, {J L} and Snyder, {R N K} and M Tanen and D Hilliard and B Weiss and P Larson and M Gutierrez and G Jiang and F. Liu and Pryor, {K A} and J Yao and L Zhu and Holst, {Jens Juul} and C Deacon and G Herman and N Thornberry and J Amatruda and D Williams-Herman and Wagner, {J A} and R SinhaRoy",
year = "2010",
month = "12",
day = "1",
doi = "10.1038/clpt.2010.184",
language = "English",
volume = "88",
pages = "801--8",
journal = "Clinical Pharmacology and Therapeutics",
issn = "0009-9236",
publisher = "JohnWiley & Sons, Inc.",
number = "6",

}

RIS

TY - JOUR

T1 - Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1

AU - Migoya, E M

AU - Bergeron, R

AU - Miller, J L

AU - Snyder, R N K

AU - Tanen, M

AU - Hilliard, D

AU - Weiss, B

AU - Larson, P

AU - Gutierrez, M

AU - Jiang, G

AU - Liu, F.

AU - Pryor, K A

AU - Yao, J

AU - Zhu, L

AU - Holst, Jens Juul

AU - Deacon, C

AU - Herman, G

AU - Thornberry, N

AU - Amatruda, J

AU - Williams-Herman, D

AU - Wagner, J A

AU - SinhaRoy, R

PY - 2010/12/1

Y1 - 2010/12/1

N2 - The aim of the study was to investigate the effects of a dipeptidyl peptidase-4 (DPP-4) inhibitor, of metformin, and of the combination of the two agents, on incretin hormone concentrations. Active and inactive (or total) incretin plasma concentrations, plasma DPP-4 activity, and preproglucagon (GCG) gene expression were determined after administration of each agent alone or in combination to mice with diet-induced obesity (DIO) and to healthy human subjects. In mice, metformin increased Gcg expression in the large intestine and elevated the plasma concentrations of inactive glucagon-like peptide 1 (GLP-1) (9-36) and glucagon. In healthy subjects, a DPP-4 inhibitor elevated both active GLP-1 and glucose dependent insulinotropic polypeptide (GIP), metformin increased total GLP-1 (but not GIP), and the combination resulted in additive increases in active GLP-1 plasma concentrations. Metformin did not inhibit plasma DPP-4 activity either in vitro or in vivo. The study results show that metformin is not a DPP-4 inhibitor but rather enhances precursor GCG expression in the large intestine, resulting in increased total GLP-1 concentrations. DPP-4 inhibitors and metformin have complementary mechanisms of action and additive effects with respect to increasing the concentrations of active GLP-1 in plasma.

AB - The aim of the study was to investigate the effects of a dipeptidyl peptidase-4 (DPP-4) inhibitor, of metformin, and of the combination of the two agents, on incretin hormone concentrations. Active and inactive (or total) incretin plasma concentrations, plasma DPP-4 activity, and preproglucagon (GCG) gene expression were determined after administration of each agent alone or in combination to mice with diet-induced obesity (DIO) and to healthy human subjects. In mice, metformin increased Gcg expression in the large intestine and elevated the plasma concentrations of inactive glucagon-like peptide 1 (GLP-1) (9-36) and glucagon. In healthy subjects, a DPP-4 inhibitor elevated both active GLP-1 and glucose dependent insulinotropic polypeptide (GIP), metformin increased total GLP-1 (but not GIP), and the combination resulted in additive increases in active GLP-1 plasma concentrations. Metformin did not inhibit plasma DPP-4 activity either in vitro or in vivo. The study results show that metformin is not a DPP-4 inhibitor but rather enhances precursor GCG expression in the large intestine, resulting in increased total GLP-1 concentrations. DPP-4 inhibitors and metformin have complementary mechanisms of action and additive effects with respect to increasing the concentrations of active GLP-1 in plasma.

KW - Adolescent

KW - Adult

KW - Animals

KW - Cross-Over Studies

KW - Dipeptidyl-Peptidase IV Inhibitors

KW - Double-Blind Method

KW - Drug Therapy, Combination

KW - Female

KW - Glucagon-Like Peptide 1

KW - Humans

KW - Male

KW - Metformin

KW - Mice

KW - Mice, Inbred C57BL

KW - Middle Aged

KW - Obesity

KW - Young Adult

U2 - 10.1038/clpt.2010.184

DO - 10.1038/clpt.2010.184

M3 - Journal article

C2 - 21048706

VL - 88

SP - 801

EP - 808

JO - Clinical Pharmacology and Therapeutics

JF - Clinical Pharmacology and Therapeutics

SN - 0009-9236

IS - 6

ER -

ID: 33938724