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Sacubitril/valsartan increases postprandial gastrin and cholecystokinin in plasma

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@article{f883a8ac67824c23ac9ab27b3e22bce4,
title = "Sacubitril/valsartan increases postprandial gastrin and cholecystokinin in plasma",
abstract = "Aims: Neprilysin degrades natriuretic peptides in circulation and is also suggested to degrade the gut hormones gastrin and cholecystokinin. Neprilysin inhibition has become a therapeutic strategy and thus a regimen in need of further testing in terms of other hormonal axes besides natriuretic peptides. The aim of this study was to examine whether acute inhibition of neprilysin affects meal-induced responses in gastrin and cholecystokinin concentrations in healthy individuals.Methods and results: Nine healthy young men were included in an open-labelled, randomized cross-over clinical trial. The participants received a standardized meal (25 g fat, 26 g protein, 42 g carbohydrate) on two separate days with or without a one-time dosage of sacubitril ((194 mg)/valsartan (206 mg)). Blood pressure, heart rate and blood samples were measured and collected during the experiment. Statistical differences between groups were assessed using area under the curve together with an ANOVA with a Bonferroni post hoc test. Sacubitril/valsartan increased the postprandial plasma concentrations of both gastrin and cholecystokinin (80% (AUC0-270 min, P = 0.004) and 60% (AUC0-270 min, P = 0.003), respectively) compared with the control meal. No significant hemodynamic effects were noted (blood pressure, AUC0-270 min, P = 0.86, heart rate, AUC0-270 min, P = 0.96).Conclusion: Our study demonstrates that sacubitril/valsartan increases the postprandial plasma concentrations of gastrin and cholecystokinin in healthy individuals. The results thus suggest that neprilysin-mediated degradation of gastrin and cholecystokinin is physiologically relevant and may have a role in heart failure patients treated with sacubitril/valsartan.",
author = "Andersen, {Ulrik {\O}} and Dijana Terzic and {Wewer Albrechtsen}, {Nicolai Jacob} and {Dall Mark}, Peter and Peter Plomgaard and Rehfeld, {Jens F} and Finn Gustafsson and Goetze, {Jens P}",
year = "2020",
month = may,
doi = "10.1530/EC-19-0563",
language = "English",
volume = "9",
pages = "438--444",
journal = "Endocrine Connections",
issn = "2049-3614",
publisher = "BioScientifica Ltd",
number = "5",

}

RIS

TY - JOUR

T1 - Sacubitril/valsartan increases postprandial gastrin and cholecystokinin in plasma

AU - Andersen, Ulrik Ø

AU - Terzic, Dijana

AU - Wewer Albrechtsen, Nicolai Jacob

AU - Dall Mark, Peter

AU - Plomgaard, Peter

AU - Rehfeld, Jens F

AU - Gustafsson, Finn

AU - Goetze, Jens P

PY - 2020/5

Y1 - 2020/5

N2 - Aims: Neprilysin degrades natriuretic peptides in circulation and is also suggested to degrade the gut hormones gastrin and cholecystokinin. Neprilysin inhibition has become a therapeutic strategy and thus a regimen in need of further testing in terms of other hormonal axes besides natriuretic peptides. The aim of this study was to examine whether acute inhibition of neprilysin affects meal-induced responses in gastrin and cholecystokinin concentrations in healthy individuals.Methods and results: Nine healthy young men were included in an open-labelled, randomized cross-over clinical trial. The participants received a standardized meal (25 g fat, 26 g protein, 42 g carbohydrate) on two separate days with or without a one-time dosage of sacubitril ((194 mg)/valsartan (206 mg)). Blood pressure, heart rate and blood samples were measured and collected during the experiment. Statistical differences between groups were assessed using area under the curve together with an ANOVA with a Bonferroni post hoc test. Sacubitril/valsartan increased the postprandial plasma concentrations of both gastrin and cholecystokinin (80% (AUC0-270 min, P = 0.004) and 60% (AUC0-270 min, P = 0.003), respectively) compared with the control meal. No significant hemodynamic effects were noted (blood pressure, AUC0-270 min, P = 0.86, heart rate, AUC0-270 min, P = 0.96).Conclusion: Our study demonstrates that sacubitril/valsartan increases the postprandial plasma concentrations of gastrin and cholecystokinin in healthy individuals. The results thus suggest that neprilysin-mediated degradation of gastrin and cholecystokinin is physiologically relevant and may have a role in heart failure patients treated with sacubitril/valsartan.

AB - Aims: Neprilysin degrades natriuretic peptides in circulation and is also suggested to degrade the gut hormones gastrin and cholecystokinin. Neprilysin inhibition has become a therapeutic strategy and thus a regimen in need of further testing in terms of other hormonal axes besides natriuretic peptides. The aim of this study was to examine whether acute inhibition of neprilysin affects meal-induced responses in gastrin and cholecystokinin concentrations in healthy individuals.Methods and results: Nine healthy young men were included in an open-labelled, randomized cross-over clinical trial. The participants received a standardized meal (25 g fat, 26 g protein, 42 g carbohydrate) on two separate days with or without a one-time dosage of sacubitril ((194 mg)/valsartan (206 mg)). Blood pressure, heart rate and blood samples were measured and collected during the experiment. Statistical differences between groups were assessed using area under the curve together with an ANOVA with a Bonferroni post hoc test. Sacubitril/valsartan increased the postprandial plasma concentrations of both gastrin and cholecystokinin (80% (AUC0-270 min, P = 0.004) and 60% (AUC0-270 min, P = 0.003), respectively) compared with the control meal. No significant hemodynamic effects were noted (blood pressure, AUC0-270 min, P = 0.86, heart rate, AUC0-270 min, P = 0.96).Conclusion: Our study demonstrates that sacubitril/valsartan increases the postprandial plasma concentrations of gastrin and cholecystokinin in healthy individuals. The results thus suggest that neprilysin-mediated degradation of gastrin and cholecystokinin is physiologically relevant and may have a role in heart failure patients treated with sacubitril/valsartan.

U2 - 10.1530/EC-19-0563

DO - 10.1530/EC-19-0563

M3 - Journal article

C2 - 32348960

VL - 9

SP - 438

EP - 444

JO - Endocrine Connections

JF - Endocrine Connections

SN - 2049-3614

IS - 5

ER -

ID: 59943988