{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T10:09:44Z","timestamp":1792922984480,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,6,14]],"date-time":"2020-06-14T00:00:00Z","timestamp":1592092800000},"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"}]},{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims\/Introduction<\/jats:title><jats:p>Recent clinical trials on sodium\u2013glucose cotransporter\u00a02 inhibitors showed improved outcomes in patients with type\u00a02 diabetes at a high risk of cardiovascular events. However, the underlying effects on endothelial function remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>The effect of empagliflozin on endothelial function in cardiovascular high risk diabetes mellitus: Multi\u2010center placebo\u2010controlled double\u2010blind randomized (EMBLEM) trial in patients with type\u00a02 diabetes and cardiovascular disease showed empagliflozin treatment for 24\u00a0weeks had no effect on peripheral endothelial function measured by reactive hyperemia peripheral arterial tonometry. This post\u2010hoc analysis of the EMBLEM trial included a detailed evaluation of the effects of empagliflozin on peripheral endothelial function in order to elucidate the clinical characteristics of responders or non\u2010responders to treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 47 patients randomized into the empagliflozin group, 21 (44.7%) showed an increase in the reactive hyperemia index (RHI) after 24\u00a0weeks of intervention, with no apparent difference in the clinical characteristics between patients whose RHI either increased (at least &gt;0) or did not increase. There was also no obvious difference between the treatment groups in the proportion of patients who had a clinically meaningful change (\u226515%) in log\u2010transformed RHI. No correlation was found between changes in RHI and clinical variables, such as vital signs and laboratory parameters.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Treatment with empagliflozin for 24\u00a0weeks in patients with type\u00a02 diabetes and cardiovascular disease did not affect peripheral endothelial function, and was not related to changes in clinical variables, including glycemic parameters. These findings suggest that the actions of sodium\u2013glucose cotransporter\u00a02 inhibitors other than direct improvement in peripheral endothelial function were responsible, at least in the early phase, for the clinical benefits found in recent cardiovascular outcome trials.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.13289","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T04:08:32Z","timestamp":1592194112000},"page":"1551-1563","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Secondary analyses to assess the profound effects of empagliflozin on endothelial function in patients with type\u00a02 diabetes and established cardiovascular diseases: The placebo\u2010controlled double\u2010blind randomized effect of empagliflozin on endothelial function in cardiovascular high risk diabetes mellitus: Multi\u2010center placebo\u2010controlled double\u2010blind randomized 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