{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T16:34:06Z","timestamp":1793205246329,"version":"4.5.0"},"reference-count":20,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To evaluate whether type 2 diabetes status modifies the efficacy and safety of combining zibotentan (zibo), a selective endothelin receptor antagonist, and dapagliflozin (dapa) compared to placebo plus dapagliflozin in individuals with chronic kidney disease (CKD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Materials<\/jats:title>\n                    <jats:p>We conducted a post hoc analysis of the ZENITH\u2010CKD trial, a multicentre 12\u2010week, double\u2010blind, randomized, active\u2010controlled, phase 2b study involving 447 participants with CKD (261 with and 186 without type 2 diabetes). Participants were assigned to zibotentan (0.25 or 1.5\u2009mg) plus dapagliflozin 10\u2009mg or placebo plus dapagliflozin 10\u2009mg. Changes in urinary albumin\u2010to\u2010creatinine ratio (UACR) and markers of fluid retention (bodyweight and B\u2010type natriuretic peptide [BNP]) were compared in participants with and without type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Zibo\/dapa 0.25\/10\u2009mg changed UACR by \u221237.7% (90% CI: \u221240.4, \u221223.4) compared to placebo\/dapa in participants without diabetes and by \u221217.9% (90% CI: \u221231.3, \u22122.0) in participants with diabetes (p\u2010interaction 0.096). Effects of zibo\/dapa 1.5\/10\u2009mg on UACR were consistent regardless of diabetes status (\u221234.0% (90% CI: \u221245.0, \u221220.8) vs. \u221233.0% (90% CI: \u221242.2, \u221222.5), p\u2010interaction 0.921). Changes in body weight and BNP did not differ by diabetes status. Fluid retention occurred in five participants with diabetes assigned to zibo\/dapa 1.5\/10\u2009mg and one participant with diabetes in the zibo\/dapa 0.25\/10\u2009mg group. Fluid retention did not occur in those without diabetes in both zibo\/dapa groups. With placebo\/dapa, fluid retention occurred in one participant without diabetes and in none with diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Combination therapy with zibotentan and dapagliflozin demonstrated consistent efficacy and safety across CKD patients with and without type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.16468","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T06:44:24Z","timestamp":1747809864000},"page":"4311-4319","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effects of combined treatment with zibotentan and dapagliflozin compared to dapagliflozin alone in patients with diabetic and non\u2010diabetic chronic kidney disease"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1822-8188","authenticated-orcid":false,"given":"Victor","family":"Wasehuus","sequence":"first","affiliation":[{"name":"Steno Diabetes Center Copenhagen  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1725-9927","authenticated-orcid":false,"given":"J. David","family":"Smeijer","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2978-1886","authenticated-orcid":false,"given":"Phil","family":"Ambery","sequence":"additional","affiliation":[{"name":"BioPharmaceuticals R&amp;D AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Greasley","sequence":"additional","affiliation":[{"name":"BioPharmaceuticals R&amp;D AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Wijkmark","sequence":"additional","affiliation":[{"name":"BioPharmaceuticals R&amp;D AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Centre for Kidney and Bladder Health University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1531-4294","authenticated-orcid":false,"given":"Peter","family":"Rossing","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen  Herlev Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-3730","authenticated-orcid":false,"given":"Hiddo J. L.","family":"Heerspink","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"},{"name":"George Institute for Global Health  Barangaroo New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.07.012"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kisu.2021.11.003"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581\u2010024\u201000820\u20106"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024816"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204233"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(23)02302\u20104"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(19)30772\u2010X"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.07040713"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.0000000000000436"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2017.02.021"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.09.026"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(23)02230\u20104"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(21)00243\u20106"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.0000000000000161"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(23)00322\u20104"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009060593"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2308550"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(21)00242\u20104"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(22)02034\u20107"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.048740"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.16468","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.16468","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.16468","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:17:25Z","timestamp":1787591845000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/10.1111\/dom.16468"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,21]]},"references-count":20,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1111\/dom.16468"],"URL":"https:\/\/doi.org\/10.1111\/dom.16468","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/DOM.16468\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.16468\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.16468\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.16468\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.16468\/v1\/review2","asserted-by":"object"}]},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,21]]},"assertion":[{"value":"2025-02-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}