Single-Dose Metformin Enhances Bile Acid-Induced Glucagon-Like Peptide-1 Secretion in Patients With Type 2 Diabetes

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Standard

Single-Dose Metformin Enhances Bile Acid-Induced Glucagon-Like Peptide-1 Secretion in Patients With Type 2 Diabetes. / Brønden, Andreas; Albér, Anders; Rohde, Ulrich; Rehfeld, Jens F; Holst, Jens J; Vilsbøll, Tina; Knop, Filip K.

In: The Journal of clinical endocrinology and metabolism, Vol. 102, No. 11, 11.2017, p. 4153-4162.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Brønden, A, Albér, A, Rohde, U, Rehfeld, JF, Holst, JJ, Vilsbøll, T & Knop, FK 2017, 'Single-Dose Metformin Enhances Bile Acid-Induced Glucagon-Like Peptide-1 Secretion in Patients With Type 2 Diabetes', The Journal of clinical endocrinology and metabolism, vol. 102, no. 11, pp. 4153-4162. https://doi.org/10.1210/jc.2017-01091

APA

Brønden, A., Albér, A., Rohde, U., Rehfeld, J. F., Holst, J. J., Vilsbøll, T., & Knop, F. K. (2017). Single-Dose Metformin Enhances Bile Acid-Induced Glucagon-Like Peptide-1 Secretion in Patients With Type 2 Diabetes. The Journal of clinical endocrinology and metabolism, 102(11), 4153-4162. https://doi.org/10.1210/jc.2017-01091

Vancouver

Brønden A, Albér A, Rohde U, Rehfeld JF, Holst JJ, Vilsbøll T et al. Single-Dose Metformin Enhances Bile Acid-Induced Glucagon-Like Peptide-1 Secretion in Patients With Type 2 Diabetes. The Journal of clinical endocrinology and metabolism. 2017 Nov;102(11):4153-4162. https://doi.org/10.1210/jc.2017-01091

Author

Brønden, Andreas ; Albér, Anders ; Rohde, Ulrich ; Rehfeld, Jens F ; Holst, Jens J ; Vilsbøll, Tina ; Knop, Filip K. / Single-Dose Metformin Enhances Bile Acid-Induced Glucagon-Like Peptide-1 Secretion in Patients With Type 2 Diabetes. In: The Journal of clinical endocrinology and metabolism. 2017 ; Vol. 102, No. 11. pp. 4153-4162.

Bibtex

@article{a881828df36c49de91016fb012f4be1c,
title = "Single-Dose Metformin Enhances Bile Acid-Induced Glucagon-Like Peptide-1 Secretion in Patients With Type 2 Diabetes",
abstract = "Context: Despite a position as the first-line pharmacotherapy in type 2 diabetes, the glucose-lowering mechanisms of metformin remain to be fully clarified. Gut-derived modes of action, including suppression of bile acid reabsorption and a resulting increase in glucagon-like peptide-1 (GLP-1) secretion, have been proposed.Objective: The aim of this study was to assess the GLP-1 secretory and glucometabolic effects of endogenously released bile, with and without concomitant single-dose administration of metformin in patients with type 2 diabetes.Design: Randomized, placebo-controlled, and double-blinded crossover study.Setting: This study was conducted at Center for Diabetes Research, Gentofte Hospital, Denmark.Patients: Fifteen metformin-treated patients with type 2 diabetes; all participants completed the study.Interventions: Four experimental study days in randomized order with administration of either 1500 mg metformin or placebo in combination with intravenous infusion of cholecystokinin (0.4 pmol × kg-1 × min-1) or saline.Main Outcome Measure: Plasma GLP-1 excursions as measured by baseline-subtracted area under the curve.Results: Single-dose metformin further enhanced bile acid-mediated induction of GLP-1 secretion (P = 0.02), whereas metformin alone did not increase plasma GLP-1 concentrations compared with placebo (P = 0.17). Metformin, both with (P = 0.02) and without (P = 0.02) concomitant cholecystokinin-induced gallbladder emptying, elicited reduced plasma glucose excursions compared with placebo. No GLP-1-mediated induction of insulin secretion or suppression of glucagon was observed.Conclusions: Metformin elicited an enhancement of the GLP-1 response to cholecystokinin-induced gallbladder emptying in patients with type 2 diabetes, whereas no derived effects on insulin or glucagon secretion were evident in this acute setting.",
keywords = "Journal Article",
author = "Andreas Br{\o}nden and Anders Alb{\'e}r and Ulrich Rohde and Rehfeld, {Jens F} and Holst, {Jens J} and Tina Vilsb{\o}ll and Knop, {Filip K}",
year = "2017",
month = "11",
doi = "10.1210/jc.2017-01091",
language = "English",
volume = "102",
pages = "4153--4162",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Oxford University Press",
number = "11",

}

RIS

TY - JOUR

T1 - Single-Dose Metformin Enhances Bile Acid-Induced Glucagon-Like Peptide-1 Secretion in Patients With Type 2 Diabetes

AU - Brønden, Andreas

AU - Albér, Anders

AU - Rohde, Ulrich

AU - Rehfeld, Jens F

AU - Holst, Jens J

AU - Vilsbøll, Tina

AU - Knop, Filip K

PY - 2017/11

Y1 - 2017/11

N2 - Context: Despite a position as the first-line pharmacotherapy in type 2 diabetes, the glucose-lowering mechanisms of metformin remain to be fully clarified. Gut-derived modes of action, including suppression of bile acid reabsorption and a resulting increase in glucagon-like peptide-1 (GLP-1) secretion, have been proposed.Objective: The aim of this study was to assess the GLP-1 secretory and glucometabolic effects of endogenously released bile, with and without concomitant single-dose administration of metformin in patients with type 2 diabetes.Design: Randomized, placebo-controlled, and double-blinded crossover study.Setting: This study was conducted at Center for Diabetes Research, Gentofte Hospital, Denmark.Patients: Fifteen metformin-treated patients with type 2 diabetes; all participants completed the study.Interventions: Four experimental study days in randomized order with administration of either 1500 mg metformin or placebo in combination with intravenous infusion of cholecystokinin (0.4 pmol × kg-1 × min-1) or saline.Main Outcome Measure: Plasma GLP-1 excursions as measured by baseline-subtracted area under the curve.Results: Single-dose metformin further enhanced bile acid-mediated induction of GLP-1 secretion (P = 0.02), whereas metformin alone did not increase plasma GLP-1 concentrations compared with placebo (P = 0.17). Metformin, both with (P = 0.02) and without (P = 0.02) concomitant cholecystokinin-induced gallbladder emptying, elicited reduced plasma glucose excursions compared with placebo. No GLP-1-mediated induction of insulin secretion or suppression of glucagon was observed.Conclusions: Metformin elicited an enhancement of the GLP-1 response to cholecystokinin-induced gallbladder emptying in patients with type 2 diabetes, whereas no derived effects on insulin or glucagon secretion were evident in this acute setting.

AB - Context: Despite a position as the first-line pharmacotherapy in type 2 diabetes, the glucose-lowering mechanisms of metformin remain to be fully clarified. Gut-derived modes of action, including suppression of bile acid reabsorption and a resulting increase in glucagon-like peptide-1 (GLP-1) secretion, have been proposed.Objective: The aim of this study was to assess the GLP-1 secretory and glucometabolic effects of endogenously released bile, with and without concomitant single-dose administration of metformin in patients with type 2 diabetes.Design: Randomized, placebo-controlled, and double-blinded crossover study.Setting: This study was conducted at Center for Diabetes Research, Gentofte Hospital, Denmark.Patients: Fifteen metformin-treated patients with type 2 diabetes; all participants completed the study.Interventions: Four experimental study days in randomized order with administration of either 1500 mg metformin or placebo in combination with intravenous infusion of cholecystokinin (0.4 pmol × kg-1 × min-1) or saline.Main Outcome Measure: Plasma GLP-1 excursions as measured by baseline-subtracted area under the curve.Results: Single-dose metformin further enhanced bile acid-mediated induction of GLP-1 secretion (P = 0.02), whereas metformin alone did not increase plasma GLP-1 concentrations compared with placebo (P = 0.17). Metformin, both with (P = 0.02) and without (P = 0.02) concomitant cholecystokinin-induced gallbladder emptying, elicited reduced plasma glucose excursions compared with placebo. No GLP-1-mediated induction of insulin secretion or suppression of glucagon was observed.Conclusions: Metformin elicited an enhancement of the GLP-1 response to cholecystokinin-induced gallbladder emptying in patients with type 2 diabetes, whereas no derived effects on insulin or glucagon secretion were evident in this acute setting.

KW - Journal Article

U2 - 10.1210/jc.2017-01091

DO - 10.1210/jc.2017-01091

M3 - Journal article

VL - 102

SP - 4153

EP - 4162

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 11

ER -

ID: 185871674