TY - JOUR
T1 - Mechanisms underlying the blood pressure-lowering effects of empagliflozin, losartan and their combination in people with type 2 diabetes
T2 - A secondary analysis of a randomized crossover trial
AU - Scholtes, Rosalie A.
AU - Mosterd, Charlotte M.
AU - Hesp, Anne C.
AU - Smits, Mark M.
AU - Heerspink, Hiddo J. L.
AU - van Raalte, Daniël H.
N1 - Funding Information: We are very grateful for the time and commitment of our study participants during times of COVID-19, without whom we could have not finished the protocol. We would also like to acknowledge the help of the assistants and technicians who were indispensable in the process of data collection: Jeanette Boerop, Ingrid Knufman, Petra de Bree and Renée de Meijer. The study medication was provided by Boehringer Ingelheim. The funder had no role in the study design, the analyses or interpretation of the data, or drafting the manuscript. The funder had no role in the decision to submit this manuscript for publication. Publisher Copyright: © 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
PY - 2023/1
Y1 - 2023/1
N2 - Aim: To study the effects of the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin, the angiotensin receptor blocker (ARB) losartan, and their combination on blood pressure, while studying the mechanisms potentially involved. Methods: A total of 24 people with type 2 diabetes (T2D) (age: 66 ± 6 years; body mass index: 31.0 ± 3 kg/m 2; estimated glomerular filtration rate: 90 ml/min/1.73m 2) received a 1-week treatment with empagliflozin 10 mg once daily, losartan 50 mg once daily, their combination, and placebo, in a randomized double-blind crossover design, with 4-week washout periods in between. Blood pressure, arterial stiffness, autonomic nervous system activity and plasma volume, extracellular fluid and serum albumin were assessed. Results: Versus placebo (139 mmHg), empagliflozin reduced systolic blood pressure (SBP) by 8 mmHg (P =.001), losartan by 12 mmHg (P =.001) and empagliflozin + losartan by 15 mmHg (P <.001). Combination therapy had a larger SBP-lowering effect versus empagliflozin monotherapy (-7 [95% CI -12; -2] mmHg) and numerically larger effects versus losartan monotherapy (-3 [-8; 2] mmHg). Empagliflozin reduced sympathetic nervous system (SNS) activity, arterial stiffness and extracellular fluid, while increasing serum albumin. Losartan reduced SNS activity and arterial stiffness. Combination therapy induced volume contraction variables, together with a reduction in SNS activity and arterial stiffness. Conclusion: In people with T2D, SGLT2 inhibition in combination with an ARB had a larger blood pressure-lowering effect versus placebo than either of the drugs alone. Our data further suggest that the mechanisms underlying these blood pressure reductions at least partially differ between these agents.
AB - Aim: To study the effects of the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin, the angiotensin receptor blocker (ARB) losartan, and their combination on blood pressure, while studying the mechanisms potentially involved. Methods: A total of 24 people with type 2 diabetes (T2D) (age: 66 ± 6 years; body mass index: 31.0 ± 3 kg/m 2; estimated glomerular filtration rate: 90 ml/min/1.73m 2) received a 1-week treatment with empagliflozin 10 mg once daily, losartan 50 mg once daily, their combination, and placebo, in a randomized double-blind crossover design, with 4-week washout periods in between. Blood pressure, arterial stiffness, autonomic nervous system activity and plasma volume, extracellular fluid and serum albumin were assessed. Results: Versus placebo (139 mmHg), empagliflozin reduced systolic blood pressure (SBP) by 8 mmHg (P =.001), losartan by 12 mmHg (P =.001) and empagliflozin + losartan by 15 mmHg (P <.001). Combination therapy had a larger SBP-lowering effect versus empagliflozin monotherapy (-7 [95% CI -12; -2] mmHg) and numerically larger effects versus losartan monotherapy (-3 [-8; 2] mmHg). Empagliflozin reduced sympathetic nervous system (SNS) activity, arterial stiffness and extracellular fluid, while increasing serum albumin. Losartan reduced SNS activity and arterial stiffness. Combination therapy induced volume contraction variables, together with a reduction in SNS activity and arterial stiffness. Conclusion: In people with T2D, SGLT2 inhibition in combination with an ARB had a larger blood pressure-lowering effect versus placebo than either of the drugs alone. Our data further suggest that the mechanisms underlying these blood pressure reductions at least partially differ between these agents.
KW - SGLT2 inhibitor
KW - angiotensin receptor blocker
KW - autonomic nervous system activity
KW - blood pressure
KW - empagliflozin
KW - losartan
KW - systemic haemodynamic function
KW - type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85139068077&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/dom.14864
DO - https://doi.org/10.1111/dom.14864
M3 - Article
C2 - 36089810
SN - 1462-8902
VL - 25
SP - 198
EP - 207
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
IS - 1
ER -