Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
E-pub ahead of print

Sacubitril/valsartan augments postprandial plasma concentrations of active GLP-1 when combined with sitagliptin in men

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{1acb23deaa8f4fe6b293119db42468c6,
title = "Sacubitril/valsartan augments postprandial plasma concentrations of active GLP-1 when combined with sitagliptin in men",
abstract = "CONTEXT: Combined inhibition of neprilysin and dipeptidyl peptidase 4 (DPP-4) has been shown to augment plasma concentrations of glucagon-like peptide-1(GLP-1) in animal models, but whether this occurs in humans is unknown.OBJECTIVE: To investigate the effects of inhibition of neprilysin by sacubitril/valsartan alone or in combination with a DPP-4 inhibitor (sitagliptin) on plasma concentrations of GLP-1 in healthy men.DESIGN: Two open-labeled crossover studies were performed in human subjects.SETTING: General community.PARTICIPANTS: Nine and 10 healthy young males were included in study 1 and study 2, respectively.INTERVENTION: Study participants received a standardized meal (34{\%} carbohydrates, 45{\%} fat, 21{\%} protein, total caloric content of 2106kJ) combined with a prior dose of either sacubitril/valsartan (194/206mg) or control in study 1, and in study 2, with a prior dose of sitagliptin (2x100mg, given ∼10 hours apart) either alone or with sacubitril/valsartan (194/206mg).MAIN OUTCOME MEASURES: Plasma concentrations of total and intact GLP-1.RESULTS: Sacubitril/valsartan increased postprandial plasma concentrations of total GLP-1 by 67{\%} (tAUC0-240min: 3929±344 vs. 2348±181 min × pmol/L P=0.0023), and increased concentrations of intact GLP-1 plasma concentrations more than sitagliptin alone (tAUC0-240min: 1021±114 vs. 660±80 min × pmol/L, P=0.01). Plasma concentrations of glucose, insulin, and GIP were not significantly (P>0.10) changed upon sacubitril/valsartan treatment.CONCLUSIONS: Sacubitril/valsartan combined with a DPP-4 inhibitor lead to markedly higher concentrations of intact GLP-1 than DPP-4 inhibition alone, supporting a role for both neprilysin and DPP-4 in the metabolism of GLP-1 in humans, a finding which may have therapeutic implications.",
author = "{Wewer Albrechtsen}, {Nicolai J} and Mark, {Peter D} and Dijana Terzic and Hansen, {Lasse H} and Andersen, {Ulrik {\O}} and Bolette Hartmann and Carr, {Richard D} and Finn Gustafsson and Deacon, {Carolyn F} and Holst, {Jens J} and Goetze, {Jens P} and Peter Plomgaard",
note = "Copyright {\circledC} 2019 Endocrine Society.",
year = "2019",
month = "5",
day = "10",
doi = "10.1210/jc.2019-00515",
language = "English",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The/Endocrine Society",

}

RIS

TY - JOUR

T1 - Sacubitril/valsartan augments postprandial plasma concentrations of active GLP-1 when combined with sitagliptin in men

AU - Wewer Albrechtsen, Nicolai J

AU - Mark, Peter D

AU - Terzic, Dijana

AU - Hansen, Lasse H

AU - Andersen, Ulrik Ø

AU - Hartmann, Bolette

AU - Carr, Richard D

AU - Gustafsson, Finn

AU - Deacon, Carolyn F

AU - Holst, Jens J

AU - Goetze, Jens P

AU - Plomgaard, Peter

N1 - Copyright © 2019 Endocrine Society.

PY - 2019/5/10

Y1 - 2019/5/10

N2 - CONTEXT: Combined inhibition of neprilysin and dipeptidyl peptidase 4 (DPP-4) has been shown to augment plasma concentrations of glucagon-like peptide-1(GLP-1) in animal models, but whether this occurs in humans is unknown.OBJECTIVE: To investigate the effects of inhibition of neprilysin by sacubitril/valsartan alone or in combination with a DPP-4 inhibitor (sitagliptin) on plasma concentrations of GLP-1 in healthy men.DESIGN: Two open-labeled crossover studies were performed in human subjects.SETTING: General community.PARTICIPANTS: Nine and 10 healthy young males were included in study 1 and study 2, respectively.INTERVENTION: Study participants received a standardized meal (34% carbohydrates, 45% fat, 21% protein, total caloric content of 2106kJ) combined with a prior dose of either sacubitril/valsartan (194/206mg) or control in study 1, and in study 2, with a prior dose of sitagliptin (2x100mg, given ∼10 hours apart) either alone or with sacubitril/valsartan (194/206mg).MAIN OUTCOME MEASURES: Plasma concentrations of total and intact GLP-1.RESULTS: Sacubitril/valsartan increased postprandial plasma concentrations of total GLP-1 by 67% (tAUC0-240min: 3929±344 vs. 2348±181 min × pmol/L P=0.0023), and increased concentrations of intact GLP-1 plasma concentrations more than sitagliptin alone (tAUC0-240min: 1021±114 vs. 660±80 min × pmol/L, P=0.01). Plasma concentrations of glucose, insulin, and GIP were not significantly (P>0.10) changed upon sacubitril/valsartan treatment.CONCLUSIONS: Sacubitril/valsartan combined with a DPP-4 inhibitor lead to markedly higher concentrations of intact GLP-1 than DPP-4 inhibition alone, supporting a role for both neprilysin and DPP-4 in the metabolism of GLP-1 in humans, a finding which may have therapeutic implications.

AB - CONTEXT: Combined inhibition of neprilysin and dipeptidyl peptidase 4 (DPP-4) has been shown to augment plasma concentrations of glucagon-like peptide-1(GLP-1) in animal models, but whether this occurs in humans is unknown.OBJECTIVE: To investigate the effects of inhibition of neprilysin by sacubitril/valsartan alone or in combination with a DPP-4 inhibitor (sitagliptin) on plasma concentrations of GLP-1 in healthy men.DESIGN: Two open-labeled crossover studies were performed in human subjects.SETTING: General community.PARTICIPANTS: Nine and 10 healthy young males were included in study 1 and study 2, respectively.INTERVENTION: Study participants received a standardized meal (34% carbohydrates, 45% fat, 21% protein, total caloric content of 2106kJ) combined with a prior dose of either sacubitril/valsartan (194/206mg) or control in study 1, and in study 2, with a prior dose of sitagliptin (2x100mg, given ∼10 hours apart) either alone or with sacubitril/valsartan (194/206mg).MAIN OUTCOME MEASURES: Plasma concentrations of total and intact GLP-1.RESULTS: Sacubitril/valsartan increased postprandial plasma concentrations of total GLP-1 by 67% (tAUC0-240min: 3929±344 vs. 2348±181 min × pmol/L P=0.0023), and increased concentrations of intact GLP-1 plasma concentrations more than sitagliptin alone (tAUC0-240min: 1021±114 vs. 660±80 min × pmol/L, P=0.01). Plasma concentrations of glucose, insulin, and GIP were not significantly (P>0.10) changed upon sacubitril/valsartan treatment.CONCLUSIONS: Sacubitril/valsartan combined with a DPP-4 inhibitor lead to markedly higher concentrations of intact GLP-1 than DPP-4 inhibition alone, supporting a role for both neprilysin and DPP-4 in the metabolism of GLP-1 in humans, a finding which may have therapeutic implications.

U2 - 10.1210/jc.2019-00515

DO - 10.1210/jc.2019-00515

M3 - Journal article

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

ER -

ID: 57664420