{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:05:27Z","timestamp":1791475527634,"version":"4.3.4"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:00:00Z","timestamp":1701129600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:00:00Z","timestamp":1701129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The Netherlands Organisation for Scientific Research","award":["VIDI (917.15.306)"],"award-info":[{"award-number":["VIDI (917.15.306)"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cardiovasc Diabetol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>This post-hoc analysis of the DELIGHT trial assessed effects of the SGLT2 inhibitor dapagliflozin on iron metabolism and markers of inflammation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Patients with type 2 diabetes and albuminuria were randomized to dapagliflozin, dapagliflozin and saxagliptin, or placebo. We measured hemoglobin, iron markers (serum iron, transferrin saturation, and ferritin), plasma erythropoietin, and inflammatory markers (urinary MCP-1 and urinary\/serum IL-6) at baseline and week 24.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>360\/461 (78.1%) participants had available biosamples. Dapagliflozin and dapagliflozin-saxagliptin, compared to placebo, increased hemoglobin by 5.7\u00a0g\/L (95%CI 4.0, 7.3; p\u2009&lt;\u20090.001) and 4.4\u00a0g\/L (2.7, 6.0; p\u2009&lt;\u20090.001) and reduced ferritin by 18.6% (8.7, 27.5; p\u2009&lt;\u20090.001) and 18.4% (8.7, 27.1; p\u2009&lt;\u20090.001), respectively. Dapagliflozin reduced urinary MCP-1\/Cr by 29.0% (14.6, 41.0; p\u2009&lt;\u20090.001) and urinary IL-6\/Cr by 26.6% (9.1, 40.7; p\u2009=\u20090.005) with no changes in other markers.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Dapagliflozin increased hemoglobin and reduced ferritin and urinary markers of inflammation, suggesting potentially important effects on iron metabolism and inflammation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>ClinicalTrials.gov NCT02547935.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12933-023-02027-8","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T16:02:58Z","timestamp":1701187378000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Effects of dapagliflozin and dapagliflozin-saxagliptin on erythropoiesis, iron and inflammation markers in patients with type 2 diabetes and chronic kidney disease: data from the DELIGHT trial"],"prefix":"10.1186","volume":"22","author":[{"given":"Akihiko","family":"Koshino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendon L.","family":"Neuen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Jongs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Pollock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Greasley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva-Marie","family":"Andersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Hammarstedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Karlsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Langkilde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Wada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiddo J.L.","family":"Heerspink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,28]]},"reference":[{"key":"2027_CR1","doi-asserted-by":"crossref","unstructured":"Babitt JL, Eisenga MF, Haase VH, Kshirsagar AV, Levin A, Locatelli F et al. Controversies in optimal anemia management: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference. Kidney int. 2021;99(6):1280\u201395.","DOI":"10.1016\/j.kint.2021.03.020"},{"issue":"7","key":"2027_CR2","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.2337\/dc08-0779","volume":"32","author":"U Mehdi","year":"2009","unstructured":"Mehdi U, Toto RD. Anemia, Diabetes, and chronic Kidney Disease. Diabetes Care. 2009;32(7):1320\u20136.","journal-title":"Diabetes Care"},{"issue":"10365","key":"2027_CR3","doi-asserted-by":"publisher","first-page":"1788","DOI":"10.1016\/S0140-6736(22)02074-8","volume":"400","author":"Nuffield Department of Population Health Renal Studies Group; SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists\u2019 Consortium","year":"2022","unstructured":"Nuffield Department of Population Health Renal Studies Group; SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists\u2019 Consortium. Impact of Diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet. 2022;400(10365):1788\u2013801.","journal-title":"Lancet"},{"issue":"3","key":"2027_CR4","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1016\/j.kint.2020.04.051","volume":"98","author":"J Li","year":"2020","unstructured":"Li J, Neal B, Perkovic V, de Zeeuw D, Neuen BL, Arnott C, et al. Mediators of the effects of canagliflozin on kidney protection in patients with type 2 Diabetes. Kidney Int. 2020;98(3):769\u201377.","journal-title":"Kidney Int"},{"issue":"4","key":"2027_CR5","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1016\/j.cmet.2021.02.016","volume":"33","author":"T Sen","year":"2021","unstructured":"Sen T, Heerspink HJL. A kidney perspective on the mechanism of action of sodium glucose co-transporter 2 inhibitors. Cell Metab. 2021;33(4):732\u20139.","journal-title":"Cell Metab"},{"key":"2027_CR6","doi-asserted-by":"crossref","unstructured":"Packer M. Mechanisms of enhanced renal and hepatic erythropoietin synthesis by sodium-glucose cotransporter 2 inhibitors. Eur Heart J. 2023:ehad235.","DOI":"10.1093\/eurheartj\/ehad235"},{"issue":"13","key":"2027_CR7","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1161\/CIRCULATIONAHA.122.060511","volume":"146","author":"KF Docherty","year":"2022","unstructured":"Docherty KF, Welsh P, Verma S, De Boer RA, O\u2019Meara E, Bengtsson O, et al. Iron Deficiency in Heart Failure and effect of Dapagliflozin: findings from DAPA-HF. 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Albuminuria-lowering effect of dapagliflozin alone and in combination with saxagliptin and effect of dapagliflozin and saxagliptin on glycaemic control in patients with type 2 Diabetes and chronic Kidney Disease (DELIGHT): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2019;7(6):429\u201341.","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"8","key":"2027_CR14","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.3109\/0886022X.2010.502609","volume":"32","author":"T Eleftheriadis","year":"2010","unstructured":"Eleftheriadis T, Liakopoulos V, Antoniadi G, Stefanidis I. Which is the best way for estimating transferrin saturation? 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Diabetes Obes Metab. 2022;24(10):1950\u20136.","journal-title":"Diabetes Obes Metab"}],"container-title":["Cardiovascular Diabetology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12933-023-02027-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12933-023-02027-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12933-023-02027-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T16:06:38Z","timestamp":1701187598000},"score":1,"resource":{"primary":{"URL":"https:\/\/cardiab.biomedcentral.com\/articles\/10.1186\/s12933-023-02027-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,28]]},"references-count":19,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["2027"],"URL":"https:\/\/doi.org\/10.1186\/s12933-023-02027-8","relation":{},"ISSN":["1475-2840"],"issn-type":[{"value":"1475-2840","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,28]]},"assertion":[{"value":"19 August 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 October 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Local ethics committees approved all study procedures for the DELIGHT trial and subsequent analyses. Consent was obtained from all study participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"A. Koshino, N. Jongs and T. Wada have no conflicts of interest.B.L. Neuen has received fees for advisory boards, scientific presentations, speaker fees, steering committee roles and travel support from the American Diabetes Association, AstraZeneca, Bayer, Boehringer and Ingelheim, Cambridge Healthcare Research, Janssen and Medscape, with all honoraria paid to his institution. C. Pollock has served on the steering committee for CREDENCE trial of canagliflozin (sponsored by Janssen Cilag) and is an advisory board member and speaker for Astra Zeneca, and a speaker for Eli Lilly and Boehringer Ingelheim. P.J. Greasley, E.-M. Anderson, A. Hammarstedt, C. Karlsson and A.M. Langkilde are employees and shareholder of AstraZeneca.H.J.L. Heerspink is supported by a VIDI (917.15.306) grant from the Netherlands Organisation for Scientific Research and has served as a consultant for AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, CSL Pharma, Fresenius, Gilead, Janssen, Merck, Mundipharma, Mitsubishi Tanabe, and Retrophin; and has received grant support from AbbVie, AstraZeneca, Boehringer Ingelheim, and Janssen.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"330"}}