{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T23:36:42Z","timestamp":1764113802600,"version":"3.46.0"},"reference-count":41,"publisher":"Georg Thieme Verlag KG","issue":"10","funder":[{"name":"Deutsche Diabetes\n                        Gesellschaft"},{"name":"Boehringer Ingelheim"},{"DOI":"10.13039\/501100001654","name":"German Academic Exchange Service\n                        London","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001654","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sodium-glucose co-transporter inhibitors significantly reduce cardiovascular\n                        mortality, hospitalization for heart failure, and improve renal outcomes\n                        regardless of diabetes status. This study investigated the effect of\n                        empagliflozin on plasma biomarkers to explore underlying mechanisms.<\/jats:p>\n                  <jats:p>Adult patients with type 2 diabetes and heart failure with either left\n                        ventricular ejection fraction\u226445% (EFFORT-1) or&gt;45% (EFFORT-2) were\n                        recruited. Patients received 25 mg empagliflozin or placebo for 48 weeks.\n                        Plasma levels of endothelin-1, galectin-3, insulin-like growth factor\n                        binding protein-7, and kidney injury molecule-1 (KIM-1) were measured at\n                        baseline and at weeks 2, 12, 24, and 48.<\/jats:p>\n                  <jats:p>A total of 63 patients were recruited, 24 in EFFORT-1 and 39 in EFFORT-2.\n                        Empagliflozin significantly reduced KIM-1 levels by 38% at week 48 in\n                        EFFORT-2 compared with placebo (95% confidence interval: \u201357%, \u201313%). No\n                        significant impact on other biomarkers was observed.<\/jats:p>\n                  <jats:p>Empagliflozin demonstrated, as shown by the decrease in KIM-1 levels, a renal\n                        tubular protective effect in heart failure patients with type 2\n                        diabetes.<\/jats:p>","DOI":"10.1055\/a-2722-8616","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T23:34:24Z","timestamp":1764113664000},"page":"486-490","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Empagliflozin in Heart Failure Patients with Type 2\n                    Diabetes: A Biomarker Perspective"],"prefix":"10.1055","volume":"133","author":[{"given":"Asmaa","family":"Elrakaybi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetology, Department of\n                    Medicine II, Medical Centre, University of Freiburg Faculty of Medicine,\n                    Freiburg, Germany"},{"name":"Department of Clinical Pharmacy, Ain Shams University,\n                    Cairo, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology I, Heart Centre,\n                    University of Freiburg Faculty of Medicine, Freiburg, Germany"},{"name":"Division of Internal Medicine, University of Basel,\n                    Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00fcnter","family":"P\u00e4th","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetology, Department of\n                    Medicine II, Medical Centre, University of Freiburg Faculty of Medicine,\n                    Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Hug","sequence":"additional","affiliation":[{"name":"Pharmacy, Medical Center \u2013 University of Freiburg,\n                    Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Seufert","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetology, Department of\n                    Medicine II, Medical Centre, University of Freiburg Faculty of Medicine,\n                    Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Laubner","sequence":"additional","affiliation":[{"name":"Berta-Ottenstein Program, Faculty of Medicine University\n                    of Freiburg Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"ref3","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1186\/s12933-018-0762-4","article-title":"Association between insulin resistance and the development of cardiovascular\n                    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                  Society of Cardiology (ESC) With the special contribution of the Heart Failure\n                    Association (HFA) of the ESC","volume":"44","author":"T A McDonagh","year":"2023","journal-title":"Eur Heart J"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1016\/j.jacbts.2020.02.004","article-title":"Mechanisms of cardiovascular benefits of sodium glucose co-transporter 2 (SGLT2)\n                    inhibitors: A state-of-the-art review","volume":"5","author":"G D Lopaschuk","year":"2020","journal-title":"JACC Basic Transl Sci"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1054\/jcaf.2003.39","article-title":"Plasma endothelin-1 levels and clinical correlates in patients with chronic\n                    heart failure","volume":"9","author":"T Kinugawa","year":"2003","journal-title":"J Card Fail"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11897-010-0004-x","article-title":"Galectin-3 in cardiac remodeling and heart failure","volume":"7","author":"R A de Boer","year":"2010","journal-title":"Curr Heart Fail Rep"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1016\/j.amjcard.2014.08.018","article-title":"Prognostic usefulness of insulin-like growth factor-binding protein 7 in heart\n                    failure with reduced ejection fraction: A novel biomarker of myocardial\n                    diastolic function?","volume":"114","author":"P U Gandhi","year":"2014","journal-title":"Am J Cardiol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1002\/clc.23359","article-title":"Renal tubular damage and worsening renal function in chronic heart failure:\n                    Clinical determinants and relation to prognosis (Bio-SHiFT study)","volume":"43","author":"M Brankovic","year":"2020","journal-title":"Clin Cardiol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/jhh.2014.36","article-title":"Myocardial remodeling in hypertension","volume":"29","author":"W Nadruz","year":"2015","journal-title":"J Hum Hypertens"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"2277","DOI":"10.1093\/eurheartj\/ehi406","article-title":"The role of NT-proBNP in the diagnostics of isolated diastolic dysfunction:\n                    Correlation with echocardiographic and invasive measurements","volume":"26","author":"C Tsch\u00f6pe","year":"2005","journal-title":"Eur Heart J"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e112394","DOI":"10.1371\/journal.pone.0112394","article-title":"The sodium-glucose co-transporter 2 inhibitor empagliflozin improves\n                    diabetes-induced vascular dysfunction in the streptozotocin diabetes rat model\n                    by interfering with oxidative stress and glucotoxicity","volume":"9","author":"M Oelze","year":"2014","journal-title":"PLoS One"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/s12933-021-01346-y","article-title":"The SGLT-2 inhibitor empagliflozin improves myocardial strain, reduces cardiac\n                    fibrosis and pro-inflammatory cytokines in non-diabetic mice treated with\n                    doxorubicin","volume":"20","author":"V Quagliariello","year":"2021","journal-title":"Cardiovasc Diabetol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"104870","DOI":"10.1016\/j.phrs.2020.104870","article-title":"Empagliflozin protects heart from inflammation and energy depletion via AMPK\n                    activation","volume":"158","author":"C N Koyani","year":"2020","journal-title":"Pharmacol Res"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1007\/s00018-010-0518-0","article-title":"Endothelin","volume":"68","author":"Y Kawanabe","year":"2011","journal-title":"Cell Mol Life Sci"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"2233","DOI":"10.1161\/01.CIR.0000144462.08345.B9","article-title":"Endothelium-restricted overexpression of human endothelin-1 causes vascular\n                    remodeling and endothelial dysfunction","volume":"110","author":"F Amiri","year":"2004","journal-title":"Circulation"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1161\/01.CIR.0000105701.98663.D4","article-title":"Conditional cardiac overexpression of endothelin-1 induces inflammation and\n                    dilated cardiomyopathy in mice","volume":"109","author":"L L Yang","year":"2004","journal-title":"Circulation"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1093\/ehjcvp\/pvad053","article-title":"The effect of SGLT2 inhibitors on the endothelium and the microcirculation: From\n                    bench to bedside and beyond","volume":"9","author":"K Dimitriadis","year":"2023","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"8189","DOI":"10.3390\/ijms21218189","article-title":"Empagliflozin inhibits basal and IL-1\u03b2-mediated MCP-1\/CCL2 and endothelin-1\n                    expression in human proximal tubular cells","volume":"21","author":"M Pirklbauer","year":"2020","journal-title":"Int J Mol Sci"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"5276","DOI":"10.1038\/s41598-018-23420-4","article-title":"Canagliflozin inhibits interleukin-1\u03b2-stimulated cytokine and chemokine\n                    secretion in vascular endothelial cells by AMP-activated protein\n                    kinase-dependent and -independent mechanisms","volume":"8","author":"S J Mancini","year":"2018","journal-title":"Sci 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magnetic resonance imaging trials","volume":"8","author":"N K Dhingra","year":"2021","journal-title":"ESC Heart Fail"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"9247574","DOI":"10.1155\/2017\/9247574","article-title":"The many roles of galectin-3, a multifaceted molecule, in innate immune\n                    responses against pathogens","volume":"2017","author":"L D\u00edaz-Alvarez","year":"2017","journal-title":"Mediators Inflamm"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1002\/ehf2.14186","article-title":"Direct actions of dapagliflozin and interactions with LCZ696 and spironolactone\n                    on cardiac fibroblasts of patients with heart failure and reduced ejection\n                    fraction","volume":"10","author":"L Ortega-Paz","year":"2023","journal-title":"ESC Heart Failure"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1016\/j.jacc.2017.06.016","article-title":"Effects of canagliflozin on cardiovascular biomarkers in older adults with type\n                    2 diabetes","volume":"70","author":"J L Januzzi","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"e000760","DOI":"10.1161\/JAHA.112.000760","article-title":"Relationship of plasma galectin-3 to renal function in patients with heart\n                    failure: Effects of clinical status, pathophysiology of heart failure, and\n                    presence or absence of heart failure","volume":"1","author":"D M Gopal","year":"2012","journal-title":"J Am Heart Assoc"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"e005133","DOI":"10.1161\/CIRCHEARTFAILURE.118.005133","article-title":"IGFBP7 (insulin-like growth factor-binding protein-7) and neprilysin inhibition\n                    in patients with heart failure","volume":"11","author":"J L Januzzi","year":"2018","journal-title":"Circ Heart Fail"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s12291-018-0790-6","article-title":"Empagliflozin attenuates renal and urinary markers of tubular epithelial cell\n                    injury in streptozotocin-induced diabetic rats","volume":"35","author":"Z Ashrafi Jigheh","year":"2020","journal-title":"Indian J Clin Biochem"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"210","DOI":"10.2337\/dc20-1889","article-title":"Insulin-like growth factor binding protein 7 predicts renal and cardiovascular\n                    outcomes in the canagliflozin cardiovascular assessment study","volume":"44","author":"J L Januzzi","year":"2021","journal-title":"Diabetes Care"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1002\/ejhf.3227","article-title":"Insulin-like growth factor binding protein-7 concentrations in chronic heart\n                    failure: Results from the EMPEROR programme","volume":"26","author":"J P Ferreira","year":"2024","journal-title":"Eur J Heart Fail"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.jchf.2022.09.004","article-title":"IGFBP-7 and outcomes in heart failure with reduced ejection fraction","volume":"11","author":"C Adamson","year":"2023","journal-title":"JACC: Heart Fail"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.1111\/dom.13301","article-title":"Effects of the SGLT-2 inhibitor dapagliflozin on glomerular and tubular injury\n                    markers","volume":"20","author":"CC J Dekkers","year":"2018","journal-title":"Diabetes Obes Metab"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1016\/j.biopha.2018.10.100","article-title":"Dapagliflozin attenuates early markers of diabetic nephropathy in\n                    fructose-streptozotocin-induced diabetes in rats","volume":"109","author":"M A Oraby","year":"2019","journal-title":"Biomed Pharmacother"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"7238","DOI":"10.1038\/s41598-020-64380-y","article-title":"Empagliflozin attenuates acute kidney injury after myocardial infarction in\n                    diabetic rats","volume":"10","author":"A Kuno","year":"2020","journal-title":"Sci Rep"}],"container-title":["Experimental and Clinical Endocrinology &amp; Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2722-8616.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T23:34:26Z","timestamp":1764113666000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2722-8616"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":41,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,11,25]]},"published-print":{"date-parts":[[2025,11]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2722-8616","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0947-7349","1439-3646"],"issn-type":[{"value":"0947-7349","type":"print"},{"value":"1439-3646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]}}}