{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:35:47Z","timestamp":1792442147984,"version":"4.5.0"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/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\/100014422","name":"Eli Lilly Japan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014422","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cardiovasc Diabetol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>While the cardioprotective benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors have been established in patients with cardiovascular disease (CVD), their advantages over other anti-diabetic drugs at earlier stages remain unclear. We compared the cardioprotective effects of empagliflozin, an SGLT2 inhibitor, with those of sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, focusing on cardiac fat accumulation, cardiac function, and cardiac metabolism in patients with early-stage type 2 diabetes mellitus (T2DM) without CVD complications.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This was a prospective, randomized, open-label, blinded-endpoint, parallel-group trial that enrolled 44 Japanese patients with T2DM. The patients were randomized for 12-week administration of empagliflozin or sitagliptin. Pericardial fat accumulation and myocardial triglyceride content were evaluated by magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. Echocardiography, <jats:sup>123<\/jats:sup>I-\u03b2-methyl-iodophenyl pentadecanoic acid myocardial scintigraphy, and laboratory tests were performed at baseline and after the 12-week treatment period.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The patients were middle-aged (50.3\u2009\u00b1\u200910.7\u00a0years, mean\u2009\u00b1\u2009standard deviation) and overweight (body mass index 29.3\u2009\u00b1\u20094.9\u00a0kg\/m<jats:sup>2<\/jats:sup>). They had a short diabetes duration (3.5\u2009\u00b1\u20093.2\u00a0years), HbA1c levels of 7.1\u2009\u00b1\u20090.8%, and preserved cardiac function (ejection fraction 73.8\u2009\u00b1\u20095.0%) with no vascular complications, except for one baseline case each of diabetic nephropathy and peripheral arterial disease. After the 12-week treatment, no differences from baseline were observed between the two groups regarding changes in pericardial, epicardial, and paracardial fat content; myocardial triglyceride content; cardiac function and mass; and cardiac fatty acid metabolism. However, considering cardiometabolic biomarkers, high-density lipoprotein cholesterol and ketone bodies, including \u03b2-hydroxybutyric acid, were significantly increased, whereas uric acid, plasma glucose, plasma insulin, and homeostasis model assessment of insulin resistance were significantly lower in the empagliflozin group than in the sitagliptin group (p\u2009&lt;\u20090.05).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Although the effects on cardiac fat and function were not statistically different between the two groups, empagliflozin exhibited superior effects on cardiometabolic biomarkers, such as uric acid, high-density lipoprotein cholesterol, ketone bodies, and insulin sensitivity. Therefore, when considering the primary preventive strategies for CVD, early supplementation with SGLT2 inhibitors may be more beneficial than DPP-4 inhibitors, even in patients with early-stage T2DM without current CVD complications.<\/jats:p>\n                <jats:p><jats:italic>Clinical Trial Registration:<\/jats:italic> UMIN000026340; registered on February 28, 2017. <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/upload.umin.ac.jp\/cgi-open-bin\/icdr_e\/ctr_view.cgi%3frecptno%3dR000030257\">https:\/\/upload.umin.ac.jp\/cgi-open-bin\/icdr_e\/ctr_view.cgi?recptno=R000030257<\/jats:ext-link><\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12933-021-01228-3","type":"journal-article","created":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T13:02:56Z","timestamp":1612270976000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["A prospective randomized study comparing effects of empagliflozin to sitagliptin on cardiac fat accumulation, cardiac function, and cardiac metabolism in patients with early-stage type 2 diabetes: the ASSET study"],"prefix":"10.1186","volume":"20","author":[{"given":"Shigenori","family":"Hiruma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumika","family":"Shigiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Hisatake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunao","family":"Mizumura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Shiraga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Hori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahisa","family":"Hirose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5432-3599","authenticated-orcid":false,"given":"Naoki","family":"Kumashiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,2]]},"reference":[{"key":"1228_CR1","doi-asserted-by":"publisher","first-page":"120","DOI":"10.2337\/diacare.2.2.120","volume":"2","author":"WB Kannel","year":"1979","unstructured":"Kannel WB, McGee DL. 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Written informed consent was obtained from all participants.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"NK received research funds from Nippon Boehringer Ingelheim Co., Ltd., and lecture fees from Takeda Pharmaceutical Company Ltd.; Ono Pharmaceutical Co., Ltd.; Mitsubishi Tanabe Pharma Corporation; and Nippon Boehringer Ingelheim Co., Ltd. TH received research funds from AstraZeneca K.K., Mitsubishi Tanabe Pharma Corporation, and Novo Nordisk Pharma Ltd., and lecture fees from Sanofi K.K.; Eli Lilly Japan K.K.; Novo Nordisk Pharma Ltd.; Sumitomo Dainippon Pharma Co., Ltd.; Ono Pharmaceutical Co., Ltd.; AstraZeneca K.K.; Mitsubishi Tanabe Pharma Corporation; and Kowa Company, Limited. All funding agencies had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. SH1, FS, SH2, SM, NS, MH, and TI declare that they have no conflicts of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"32"}}