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In the current report we aim to study the characteristics, cardio-renal outcomes and the effect of empagliflozin in patients with MetS enrolled in the EMPA-REG OUTCOME trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 7020 patients with T2D and atherosclerotic cardiovascular disease were treated with empagliflozin (10\u00a0mg or 25\u00a0mg) or placebo for a median of 3.1\u00a0years. The World Health Organization MetS criteria could be determined for 6985 (99.5%) patients. We assessed the association between baseline MetS and multiple cardio-renal endpoints using Cox regression models, and we studied the change in the individual component over time of the MetS using mixed effect models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MetS at baseline was present in 5740 (82%) patients; these were more often white and had more often albuminuria and heart failure, had lower eGFR and HDL-cholesterol, and higher blood pressure, body mass index, waist circumference, and triglycerides. In the placebo group, patients with MetS had a higher risk of all outcomes including cardiovascular death: HR\u2009=\u20091.73 (95% CI\u20091.01\u20132.98), heart failure hospitalization: HR\u2009=\u20092.64 (95% CI\u20091.22, 5.72), and new or worsening nephropathy: HR\u2009=\u20093.11 (95% CI\u20092.17\u20134.46). The beneficial effect of empagliflozin was consistent on all cardio-renal outcomes regardless of presence of MetS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A large proportion of the EMPA-REG OUTCOME population fulfills the criteria for MetS. Those with MetS had increased risk of adverse cardio-renal outcomes. Compared with placebo, empagliflozin improved cardio-renal outcomes in patients with and without MetS.<\/jats:p>\n                    <jats:p>\n                      <jats:italic>Trial registration<\/jats:italic>\n                      Clinical Trial Registration: URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      . Unique identifier: NCT 01131676\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12933-020-01174-6","type":"journal-article","created":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T12:03:05Z","timestamp":1606392185000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Metabolic syndrome in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a post hoc analyses of the EMPA-REG OUTCOME trial"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2304-6138","authenticated-orcid":false,"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"first","affiliation":[]},{"given":"Subodh","family":"Verma","sequence":"additional","affiliation":[]},{"given":"David","family":"Fitchett","sequence":"additional","affiliation":[]},{"given":"Anne Pernille","family":"Ofstad","sequence":"additional","affiliation":[]},{"given":"Sabine","family":"Lauer","sequence":"additional","affiliation":[]},{"given":"Isabella","family":"Zwiener","sequence":"additional","affiliation":[]},{"given":"Jyothis","family":"George","sequence":"additional","affiliation":[]},{"given":"Christoph","family":"Wanner","sequence":"additional","affiliation":[]},{"given":"Bernard","family":"Zinman","sequence":"additional","affiliation":[]},{"given":"Silvio E.","family":"Inzucchi","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2020,11,26]]},"reference":[{"key":"1174_CR1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.trsl.2017.01.001","volume":"183","author":"JD Tune","year":"2017","unstructured":"Tune JD, Goodwill AG, Sassoon DJ, Mather KJ. 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An independent ethics committee or institutional review board approved the clinical protocol at every participating center.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All patients provided written informed consent before study entry.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"J.P.F. has received travelling fees from Behringer Ingelheim.\u00a0S.V. is President of the Canadian Medical and Surgical Knowledge Translation Research\u00a0Group, a federally incorporated not-for-profit physician organization; holds a Tier 1 Canada\u00a0Research Chair in Cardiovascular Surgery; S.V. has also received grants and personal fees for\u00a0speaker honoraria and advisory board participation from AstraZeneca, Bayer, Boehringer\u00a0Ingelheim, Janssen, and Merck. He has received grants and personal fees for advisory board\u00a0participation from Amgen, grants from Bristol-Myers Squibb, personal fees for speaker\u00a0honoraria and advisory board participation from Eli Lilly, Novo Nordisk and Sanofi, and\u00a0personal fees for speaker honoraria from EOCI Pharmacomm Ltd, Novartis, Sun\u00a0Pharmaceuticals and Toronto Knowledge Translation Working Group.\u00a0D.H.F. has received honoraria from Amgen, AstraZeneca, BI, Eli Lilly and Company, Merck\u00a0& Co., and Sanofi.\u00a0C.W. has received honoraria for consultancy and lecturing from AstraZeneca, Bayer, BI,\u00a0GlaxoSmithKline, Eli Lilly and Company, Merck Sharp & Dome, Mundipharma, Sanofi\u00a0Genzyme, and Takeda.\u00a0B.Z. has received research grants awarded to his institution from BI, AstraZeneca and Novo\u00a0Nordisk, and honoraria from Janssen, Sanofi, Eli Lilly and Company, BI, Novo Nordisk and\u00a0Merck Sharp & Dome.\u00a0S.E.I. has consulted and\/or served on Clinical Trial Steering\/Executive\/Publications\u00a0Committees for Boehringer Ingelheim (BI), AstraZeneca, Novo Nordisk, Sanofi\/Lexicon\u00a0Pharmaceuticals, Merck and Abbott. A.P.O, I.Z. and J.T.G. are employees of Boehringer\u00a0Ingelheim.\u00a0S.L. has received honoraria for consultancy from BI and F. Hoffmann La Roche.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"200"}}