{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:14:10Z","timestamp":1791000850021,"version":"4.1.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,1,13]],"date-time":"2017-01-13T00:00:00Z","timestamp":1484265600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,1,13]],"date-time":"2017-01-13T00:00:00Z","timestamp":1484265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"AstraZeneca K.K"},{"DOI":"10.13039\/100004324","name":"Astellas Pharma Inc.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004324","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100012781","name":"MSD K.K.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012781","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ono Pharmceutical Co., Ltd."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cardiovasc Diabetol"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been reported to increase both low-density lipoprotein (LDL) and high-density lipoprotein (HDL)-cholesterol (C). This study aimed to determine how SGLT-2 inhibitors affect LDL and HDL-C subspecies.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This single center, open-label, randomized, prospective study included 80 patients with type 2 diabetes taking prescribed oral hypoglycemic agents. Patients were allocated to receive dapagliflozin (n\u00a0=\u00a040) or sitagliptin (n\u00a0=\u00a040) as add-on treatment. Fasting blood samples were collected before and 12\u00a0weeks after this intervention. Small dense (sd) LDL-C, large buoyant (lb) LDL-C, HDL2-C, and HDL3-C levels were determined using our established homogeneous assays. Statistical comparison of blood parameters before and after treatment was performed using the paired <jats:italic>t<\/jats:italic> test.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Dapagliflozin and sitagliptin comparably decreased HbA1c (0.75 and 0.63%, respectively). Dapagliflozin significantly decreased body weight, systolic blood pressure, plasma triglycerides and liver transaminases, and increased adiponectin; sitagliptin did not alter these measurements. LDL-C and apolipoprotein (apo) B were not significantly changed by dapagliflozin, whereas HDL-C and apo AI were increased. Dapagliflozin did not alter concentrations of LDL-C, but sd LDL-C decreased by 20% and lb LDL-C increased by 18%. Marked elevation in lb LDL-C (53%) was observed in individuals (n\u00a0=\u00a020) whose LDL-C was elevated by dapagliflozin. However, sd LDL-C remained suppressed (20%). Dapagliflozin increased HDL2-C by 18% without affecting HDL3-C. Sitagliptin did not alter plasma lipids or lipoprotein subspecies.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>A SGLT-2 inhibitor, dapagliflozin suppresses potent atherogenic sd LDL-C and increased HDL2-C, a favorable cardiometabolic marker. Although LDL-C levels are elevated by treatment with dapagliflozin, this was due to increased concentrations of the less atherogenic lb LDL-C. However, these findings were not observed after treatment with dipeptidyl peptidase-4 inhibitor, sitagliptin.<\/jats:p>\n                <jats:p><jats:italic>Trial registration<\/jats:italic> UMIN Clinical Trials Registry (UMIN000020984)<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12933-016-0491-5","type":"journal-article","created":{"date-parts":[[2017,1,13]],"date-time":"2017-01-13T14:33:51Z","timestamp":1484318031000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":145,"title":["Dapagliflozin decreases small dense low-density lipoprotein-cholesterol and increases high-density lipoprotein 2-cholesterol in patients with type 2 diabetes: comparison with sitagliptin"],"prefix":"10.1186","volume":"16","clinical-trial-number":[{"clinical-trial-number":"umin000020984","registry":"10.18810\/umin-japan"}],"author":[{"given":"Toshiyuki","family":"Hayashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyasu","family":"Fukui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Nakanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saki","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Tomoyasu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Osamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Ohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuki","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Hirano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,1,13]]},"reference":[{"key":"491_CR1","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s40265-014-0337-y","volume":"75","author":"AJ Scheen","year":"2015","unstructured":"Scheen AJ. 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In Result (P.3), Table 1 (P.4), Table 5 (P.9) and Supplementary Table 1, the correct unit for adiponectin was \u03bcg\/mL. In Table 1 (P.4), the correct value for the post treatment body weight in dapagliflozin was 76.2\u00b114.8. In Table 6 (P.10), the correct value for the pre treatment sd LDL\/LDL-C in decreased LDL-C group was 0.38\u00b10.10.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"8"}}