{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:34:42Z","timestamp":1793406882740,"version":"4.5.0"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T00:00:00Z","timestamp":1664236800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To study the effects of the sodium\u2010glucose co\u2010transporter\u20102 (SGLT2) inhibitor empagliflozin, the angiotensin receptor blocker (ARB) losartan, and their combination on blood pressure, while studying the mechanisms potentially involved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 24 people with type 2 diabetes (T2D) (age: 66\u2009\u00b1\u20096\u2009years; body mass index: 31.0\u2009\u00b1\u20093\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ; estimated glomerular filtration rate: 90\u2009ml\/min\/1.73m\n                      <jats:sup>2<\/jats:sup>\n                      ) received a 1\u2010week treatment with empagliflozin 10\u2009mg once daily, losartan 50\u2009mg once daily, their combination, and placebo, in a randomized double\u2010blind crossover design, with 4\u2010week washout periods in between. Blood pressure, arterial stiffness, autonomic nervous system activity and plasma volume, extracellular fluid and serum albumin were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Versus placebo (139\u2009mmHg), empagliflozin reduced systolic blood pressure (SBP) by 8\u2009mmHg (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.001), losartan by 12\u2009mmHg (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.001) and empagliflozin\u2009+ losartan by 15\u2009mmHg (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.001). Combination therapy had a larger SBP\u2010lowering effect versus empagliflozin monotherapy (\u20107 [95% CI \u201012; \u20102] mmHg) and numerically larger effects versus losartan monotherapy (\u20103 [\u20108; 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In people with T2D, SGLT2 inhibition in combination with an ARB had a larger blood pressure\u2010lowering 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14864","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T02:08:58Z","timestamp":1662948538000},"page":"198-207","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Mechanisms underlying the blood pressure\u2010lowering effects of empagliflozin, losartan and their combination in people with type 2 diabetes: A secondary analysis of a randomized crossover trial"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2794-2263","authenticated-orcid":false,"given":"Rosalie A.","family":"Scholtes","sequence":"first","affiliation":[{"name":"Diabetes Center, Department of Internal Medicine Amsterdam University Medical Centers  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte M.","family":"Mosterd","sequence":"additional","affiliation":[{"name":"Diabetes Center, Department of Internal Medicine Amsterdam University Medical Centers  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne C.","family":"Hesp","sequence":"additional","affiliation":[{"name":"Diabetes Center, Department of Internal Medicine Amsterdam University Medical Centers  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark M.","family":"Smits","sequence":"additional","affiliation":[{"name":"Diabetes Center, Department of Internal Medicine Amsterdam University Medical Centers  Amsterdam The Netherlands"},{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-3730","authenticated-orcid":false,"given":"Hiddo J. 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