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Whether the therapeutic impact of SGLT2 inhibitors on clinical parameters differs according to the use of metformin therapy however remains unclear.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The study was a post hoc analysis of the EMBLEM trial (UMIN000024502). All participants (n\u2009=\u2009105; women 31.4%; mean age 64.8\u00a0years) had both T2D and CVD and were randomized to either 24\u00a0weeks of empagliflozin 10\u00a0mg daily or placebo. Analysis of the data assessed the effect of empagliflozin on changes from baseline to 24\u00a0weeks in glycemic and non-glycemic clinical parameters, according to the baseline use of metformin.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Overall, 53 (50.5%) patients received baseline metformin. In the 52 patients treated with empagliflozin (48.1% with baseline metformin), the decrease in systolic blood pressure from baseline levels was greater in patients receiving metformin, compared to that observed in metformin-na\u00efve patients (group difference \u2212 8.5 [95% confidence interval (CI) \u2212 17.7 to 0.6\u00a0mmHg], <jats:italic>p<\/jats:italic>\u2009=\u20090.066). Reduction in body mass index (BMI) was significantly greater in patients receiving baseline metformin, relative to nonusers (\u2212 0.54 [95% CI \u2212 1.07 to \u2212 0.01] kg\/m<jats:sup>2<\/jats:sup>, <jats:italic>p<\/jats:italic>\u2009=\u20090.047). The group ratio (baseline metformin users vs. nonusers) of proportional changes in the geometric mean of high-sensitivity Troponin-I (hs-TnI) was 0.74 (95% CI 0.59 to 0.92, <jats:italic>p<\/jats:italic>\u2009=\u20090.009). No obvious differences were observed in glycemic parameters (fasting plasma glucose, glycohemoglobin, and glycoalbumin) between the baseline metformin users and nonusers.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our findings suggest 24\u00a0weeks of empagliflozin treatment was associated with an improvement in glycemic control, irrespective of the baseline use of metformin therapy. The effects of empagliflozin on reductions in BMI and hs-TnI were more apparent in patients who received baseline metformin therapy, compared to that observed in metformin-na\u00efve patients.<\/jats:p>\n                <jats:p><jats:italic>Trial registration<\/jats:italic> University Medical Information Network Clinical Trial Registry, number 000024502<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12933-021-01352-0","type":"journal-article","created":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T13:02:53Z","timestamp":1627736573000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Comparison of the clinical effect of empagliflozin on glycemic and non-glycemic parameters in Japanese patients with type 2 diabetes and cardiovascular disease treated with or without baseline metformin"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3352-7661","authenticated-orcid":false,"given":"Atsushi","family":"Tanaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michio","family":"Shimabukuro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Teragawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Okada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshinari","family":"Takamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isao","family":"Taguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Toyoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Tomiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Ueda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukihito","family":"Higashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Node","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the EMBLEM Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,31]]},"reference":[{"issue":"Suppl 1","key":"1352_CR1","first-page":"S111","volume":"44","author":"Pharmacologic Approaches to Glycemic Treatment","year":"2021","unstructured":"Pharmacologic Approaches to Glycemic Treatment. 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Cardiovasc Diabetol. 2020;19(1):206.","journal-title":"Cardiovasc Diabetol"}],"container-title":["Cardiovascular Diabetology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12933-021-01352-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12933-021-01352-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12933-021-01352-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T14:04:40Z","timestamp":1627740280000},"score":1,"resource":{"primary":{"URL":"https:\/\/cardiab.biomedcentral.com\/articles\/10.1186\/s12933-021-01352-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,31]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1352"],"URL":"https:\/\/doi.org\/10.1186\/s12933-021-01352-0","relation":{},"ISSN":["1475-2840"],"issn-type":[{"value":"1475-2840","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,31]]},"assertion":[{"value":"18 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The ethical committees of the participating institutions approved the study protocol. Written, informed consent for participation in the study was obtained from all the subjects. This trial was performed in accordance with the Helsinki Declaration of 1964, and its later amendments.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors have read and approved the submission of the manuscript. The manuscript has not been published and is not being considered for publication elsewhere, in whole or in part, in any language. If the manuscript is accepted, we approve it for publication in Cardiovascular Diabetology.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"AT received honoraria from Boehringer Ingelheim and research funding from GlaxoSmithKline. MS received honorarium and an endowed chair from Boehringer Ingelheim. HirokT received lecture fees from Bayer, Boehringer Ingelheim, Daiichi Sankyo, Kowa, Takeda, Mitsubishi Tanabe, and Sanwa Kagaku Kenkyusyo. YO received lecture fees from Astellas, AstraZeneca, MSD, Ono, Mitsubishi Tanabe, Bayer, Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Daiichi Sankyo, Kissei, Novartis, Kowa, and Sanwa Kagaku Kenkyusho and research funds from Kowa and Mitsubishi Tanabe. TT received honoraria for lecturing from MSD, Sumitomo Dainippon, and Mitsubishi Tanabe, research funds from Kowa, Mitsubishi Tanabe, and Taisho, and scholarships from Astellas, Novo Nordisk, Ono, and Takeda. HirofT received research funding from Omron Health Care, Asahi Calpis Wellness, and Teijin. SU received research grants from Bristol-Myers Squibb and Kowa, non-purpose research grants from Bristol-Myers Squibb, Chugai, MSD, Pfizer, and Takeda and lecture fees from Boehringer Ingelheim and MSD. YH received consulting fees from Mitsubishi Tanabe related to this study, as well as honoraria and grants from Teijin, Boehringer Ingelheim, MSD, Sanofi, AstraZeneca, Kyowa Hakko Kirin, Takeda, Astellas, Daiichi Sankyo, Mochida, Nihon Kohden, Shionogi, Nippon Sigmax, Sanwa Kagaku Kenkyusho, Unex, and Kao and honoraria from Radiometer, Omron, Sumitomo Dainippon, Otsuka, Torii, Kowa, Fujiyakuhin, Amgen, Nippon Shinyaku, Itamar, Bayer, Eli Lilly, and Ono. KN received research grants from Asahi Kasei, Astellas, Bayer, Boehringer Ingelheim, Mitsubishi Tanabe, Teijin, and Terumo, scholarships from Astellas, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Daiichi Sankyo Healthcare, Takeda, and Teijin and personal fees from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo Healthcare, Eli Lilly, Kowa, Mitsubishi Tanabe, MSD, Novartis, Ono, Takeda, and Teijin. All other authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"160"}}