Sacubitril/Valsartan Augments Postprandial Plasma Concentrations of Active GLP-1 When Combined With Sitagliptin in Men
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Sacubitril/Valsartan Augments Postprandial Plasma Concentrations of Active GLP-1 When Combined With Sitagliptin in Men. / Wewer Albrechtsen, Nicolai J; Mark, Peter D; Terzic, Dijana; Hansen, Lasse H; Andersen, Ulrik Ø; Hartmann, Bolette; Carr, Richard D; Gustafsson, Finn; Deacon, Carolyn F; Holst, Jens J; Goetze, Jens P; Plomgaard, Peter.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 104, No. 9, 2019, p. 3868-3876.Research output: Contribution to journal › Journal article › Research › peer-review
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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
PY - 2019
Y1 - 2019
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
C2 - 31074791
VL - 104
SP - 3868
EP - 3876
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 9
ER -
ID: 219534620