The effects of empagliflozin on systemic haemodynamic function: three randomized, placebo-controlled trials

Steffen F. Nielsen; Camilla L. Duus; Niels Henrik Buus; Jesper N. Bech; Frank H. Mose

doi:10.1097/HJH.0000000000004007

The effects of empagliflozin on systemic haemodynamic function: three randomized, placebo-controlled trials

Steffen F. Nielsen^*, Camilla L. Duus, Niels Henrik Buus, Jesper N. Bech, Frank H. Mose

^*Corresponding author for this work

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Abstract

Background: Sodium glucose cotransporter 2 inhibitors lower blood pressure. The underlying mechanisms are multifactorial and include effects on vascular function. We examined the systemic hemodynamic effects of empagliflozin in patients with type 2 diabetes mellitus (DM2) with and without chronic kidney disease (CKD) and in patients with nondiabetic CKD. Methods: Three double-blinded, randomized, placebo-controlled cross-over trials, including patients with DM2 and preserved renal function (n = 16), DM2 and CKD (n = 17) and nondiabetic CKD (n = 16). Participants were randomized to 4 weeks of empagliflozin 10 mg or placebo and crossed over after a 2-week washout. We measured brachial and central 24-h ambulatory blood pressure (ABP), pulse wave velocity (PWV), augmentation index (AIx@75), markers of nitric oxide and erythrocyte sodium sensitivity (ESS), a marker of endothelial glycocalyx function. Results: Empagliflozin reduced PWV [-0.16 m/s, 95% confidence interval (95% CI): -0.26; -0.06, P = 0.002], AIx@75 (-2.17%, 95% CI: -3.31; -1.02, P < 0.001) and brachial and central ABP in the combined study population (n = 49). Changes in PWV and AIx@75 correlated to changes in systolic brachial ABP. Markers of nitric oxide did not increase, but empagliflozin decreased ESS, which was correlated to an increase in haematocrit. Conclusion: Empagliflozin decreased arterial stiffness, mediated partly by a decrease in brachial ABP. We found no increase in nitric oxide activity, but ESS decreased. While this may be explained partly by a change in haematocrit, it could indicate an improvement in endothelial glycocalyx function.

Original language	English
Journal	Journal of Hypertension
Volume	43
Issue	6
Pages (from-to)	1021-1029
Number of pages	9
ISSN	0263-6352
DOIs	https://doi.org/10.1097/HJH.0000000000004007
Publication status	Published - 1 Jun 2025

Keywords

augmentation index
blood pressure
chronic kidney disease
endothelium
nitric oxide
pulse wave velocity
sodium glucose cotransporter 2 inhibitors
type 2 diabetes mellitus

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10.1097/HJH.0000000000004007

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@article{18c37fb106d241fa930fb40cf50e8ce7,

title = "The effects of empagliflozin on systemic haemodynamic function: three randomized, placebo-controlled trials",

abstract = "Background: Sodium glucose cotransporter 2 inhibitors lower blood pressure. The underlying mechanisms are multifactorial and include effects on vascular function. We examined the systemic hemodynamic effects of empagliflozin in patients with type 2 diabetes mellitus (DM2) with and without chronic kidney disease (CKD) and in patients with nondiabetic CKD. Methods: Three double-blinded, randomized, placebo-controlled cross-over trials, including patients with DM2 and preserved renal function (n = 16), DM2 and CKD (n = 17) and nondiabetic CKD (n = 16). Participants were randomized to 4 weeks of empagliflozin 10 mg or placebo and crossed over after a 2-week washout. We measured brachial and central 24-h ambulatory blood pressure (ABP), pulse wave velocity (PWV), augmentation index (AIx@75), markers of nitric oxide and erythrocyte sodium sensitivity (ESS), a marker of endothelial glycocalyx function. Results: Empagliflozin reduced PWV [-0.16 m/s, 95% confidence interval (95% CI): -0.26; -0.06, P = 0.002], AIx@75 (-2.17%, 95% CI: -3.31; -1.02, P < 0.001) and brachial and central ABP in the combined study population (n = 49). Changes in PWV and AIx@75 correlated to changes in systolic brachial ABP. Markers of nitric oxide did not increase, but empagliflozin decreased ESS, which was correlated to an increase in haematocrit. Conclusion: Empagliflozin decreased arterial stiffness, mediated partly by a decrease in brachial ABP. We found no increase in nitric oxide activity, but ESS decreased. While this may be explained partly by a change in haematocrit, it could indicate an improvement in endothelial glycocalyx function.",

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author = "Nielsen, {Steffen F.} and Duus, {Camilla L.} and Buus, {Niels Henrik} and Bech, {Jesper N.} and Mose, {Frank H.}",

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The effects of empagliflozin on systemic haemodynamic function: three randomized, placebo-controlled trials. / Nielsen, Steffen F.; Duus, Camilla L.; Buus, Niels Henrik et al.
In: Journal of Hypertension, Vol. 43, No. 6, 01.06.2025, p. 1021-1029.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - The effects of empagliflozin on systemic haemodynamic function

T2 - three randomized, placebo-controlled trials

AU - Nielsen, Steffen F.

AU - Duus, Camilla L.

AU - Buus, Niels Henrik

AU - Bech, Jesper N.

AU - Mose, Frank H.

PY - 2025/6/1

Y1 - 2025/6/1

N2 - Background: Sodium glucose cotransporter 2 inhibitors lower blood pressure. The underlying mechanisms are multifactorial and include effects on vascular function. We examined the systemic hemodynamic effects of empagliflozin in patients with type 2 diabetes mellitus (DM2) with and without chronic kidney disease (CKD) and in patients with nondiabetic CKD. Methods: Three double-blinded, randomized, placebo-controlled cross-over trials, including patients with DM2 and preserved renal function (n = 16), DM2 and CKD (n = 17) and nondiabetic CKD (n = 16). Participants were randomized to 4 weeks of empagliflozin 10 mg or placebo and crossed over after a 2-week washout. We measured brachial and central 24-h ambulatory blood pressure (ABP), pulse wave velocity (PWV), augmentation index (AIx@75), markers of nitric oxide and erythrocyte sodium sensitivity (ESS), a marker of endothelial glycocalyx function. Results: Empagliflozin reduced PWV [-0.16 m/s, 95% confidence interval (95% CI): -0.26; -0.06, P = 0.002], AIx@75 (-2.17%, 95% CI: -3.31; -1.02, P < 0.001) and brachial and central ABP in the combined study population (n = 49). Changes in PWV and AIx@75 correlated to changes in systolic brachial ABP. Markers of nitric oxide did not increase, but empagliflozin decreased ESS, which was correlated to an increase in haematocrit. Conclusion: Empagliflozin decreased arterial stiffness, mediated partly by a decrease in brachial ABP. We found no increase in nitric oxide activity, but ESS decreased. While this may be explained partly by a change in haematocrit, it could indicate an improvement in endothelial glycocalyx function.

AB - Background: Sodium glucose cotransporter 2 inhibitors lower blood pressure. The underlying mechanisms are multifactorial and include effects on vascular function. We examined the systemic hemodynamic effects of empagliflozin in patients with type 2 diabetes mellitus (DM2) with and without chronic kidney disease (CKD) and in patients with nondiabetic CKD. Methods: Three double-blinded, randomized, placebo-controlled cross-over trials, including patients with DM2 and preserved renal function (n = 16), DM2 and CKD (n = 17) and nondiabetic CKD (n = 16). Participants were randomized to 4 weeks of empagliflozin 10 mg or placebo and crossed over after a 2-week washout. We measured brachial and central 24-h ambulatory blood pressure (ABP), pulse wave velocity (PWV), augmentation index (AIx@75), markers of nitric oxide and erythrocyte sodium sensitivity (ESS), a marker of endothelial glycocalyx function. Results: Empagliflozin reduced PWV [-0.16 m/s, 95% confidence interval (95% CI): -0.26; -0.06, P = 0.002], AIx@75 (-2.17%, 95% CI: -3.31; -1.02, P < 0.001) and brachial and central ABP in the combined study population (n = 49). Changes in PWV and AIx@75 correlated to changes in systolic brachial ABP. Markers of nitric oxide did not increase, but empagliflozin decreased ESS, which was correlated to an increase in haematocrit. Conclusion: Empagliflozin decreased arterial stiffness, mediated partly by a decrease in brachial ABP. We found no increase in nitric oxide activity, but ESS decreased. While this may be explained partly by a change in haematocrit, it could indicate an improvement in endothelial glycocalyx function.

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KW - blood pressure

KW - chronic kidney disease

KW - endothelium

KW - nitric oxide

KW - pulse wave velocity

KW - sodium glucose cotransporter 2 inhibitors

KW - type 2 diabetes mellitus

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JO - Journal of Hypertension

JF - Journal of Hypertension

IS - 6

ER -

The effects of empagliflozin on systemic haemodynamic function: three randomized, placebo-controlled trials

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