{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:27:36Z","timestamp":1790616456273,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009947","name":"Merck Sharp and Dohme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009947","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Cardiology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>A recent meta\u2010analysis of sodium\u2013glucose cotransporter 2 (SGLT2) inhibitor outcome trials reported that SGLT2 inhibitors were associated with reduction in the risk of adverse composite kidney outcomes, with moderate heterogeneity across the trials; however, the endpoints were defined differently across the trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis<\/jats:title>\n                    <jats:p>The apparent heterogeneity of the meta\u2010analysis of kidney composite outcomes of SGLT2 inhibitor trials will be substantially reduced by using a consistent assessment of sustained \u226540% decline in eGFR\/chronic kidney dialysis\/transplantation\/renal death across trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a meta\u2010analysis of kidney composite outcomes from the four SGLT2 cardiovascular outcome trial programs conducted in general type 2 diabetes mellitus populations, which included, as a surrogate of progression to kidney failure, a sustained \u226540% decline in eGFR along with kidney replacement therapy and kidney death. The trials assessed were VERTIS CV (NCT01986881), CANVAS Program (NCT01032629 and NCT01989754), DECLARE\u2010TIMI 58 (NCT01730534), and EMPA\u2010REG OUTCOME (NCT01131676).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Data from the trials comprised 42\u2009516 individual participants; overall, 998 composite kidney events occurred. SGLT2 inhibition was associated with a significant reduction in the kidney composite endpoint (HR 0.58 [95% CI 0.51\u20130.65]) and with a highly consistent effect across the trials (Q statistic p\u00a0=\u00a0.64;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u20090.0%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our meta\u2010analysis highlights the value of using similarly defined endpoints across trials and supports the finding of consistent protection against kidney disease progression with SGLT2 inhibitors as a class in patients with type 2 diabetes mellitus who either have established atherosclerotic cardiovascular disease or are at high cardiovascular risk with multiple cardiovascular risk factors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/clc.23665","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T08:46:43Z","timestamp":1623746803000},"page":"1139-1143","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Kidney outcomes using a sustained \u226540% decline in\n                    <scp>eGFR<\/scp>\n                    : A meta\u2010analysis of\n                    <scp>SGLT2<\/scp>\n                    inhibitor trials"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4164-0429","authenticated-orcid":false,"given":"David Z. I.","family":"Cherney","sequence":"first","affiliation":[{"name":"Division of Nephrology University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Dagogo\u2010Jack","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren K.","family":"McGuire","sequence":"additional","affiliation":[{"name":"Division of Cardiology University of Texas Southwestern Medical Center, and Parkland Health and Hospital System  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Cosentino","sequence":"additional","affiliation":[{"name":"Unit of Cardiology Karolinska Institute and Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Pratley","sequence":"additional","affiliation":[{"name":"AdventHealth Translational Research Institute  Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weichung J.","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Epidemiology Rutgers School of Public Health and Rutgers Cancer Institute of New Jersey  New Brunswick New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Frederich","sequence":"additional","affiliation":[{"name":"Clinical Development and Operations Research and Development, Pfizer Inc.  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Maldonado","sequence":"additional","affiliation":[{"name":"Diabetes and Endocrinology MSD Limited  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Global Product Development Statistics Merck &amp; Co., Inc.  Kenilworth New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Wang","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4596-2791","authenticated-orcid":false,"given":"Christopher P.","family":"Cannon","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the VERTIS CV Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,15]]},"reference":[{"issue":"2","key":"e_1_2_10_2_1","first-page":"148","article-title":"Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: a meta\u2010analysis","volume":"6","author":"DK MG","year":"2020","journal-title":"JAMA Cardiol."},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2004967"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.07.013"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2014.07.030"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-021-05407-5"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812389"},{"key":"e_1_2_10_9_1","first-page":"2103","article-title":"Choice of endpoint in kidney outcome trials: considerations from the EMPA\u2010REG OUTCOME\u00ae trial","volume":"35","author":"Perkovic V","year":"2020","journal-title":"Nephrol Dialysis Transplantation Off Pub European Dialysis Transplant Assoc European Renal Assoc"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.2307\/2332378"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1186"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1515920"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.06.024"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.020053"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(18)30141-4"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(19)30180-9"}],"container-title":["Clinical Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/clc.23665","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/clc.23665","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/clc.23665","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T19:31:24Z","timestamp":1693337484000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/clc.23665"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,15]]},"references-count":16,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1002\/clc.23665"],"URL":"https:\/\/doi.org\/10.1002\/clc.23665","archive":["Portico"],"relation":{},"ISSN":["0160-9289","1932-8737"],"issn-type":[{"value":"0160-9289","type":"print"},{"value":"1932-8737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,15]]},"assertion":[{"value":"2021-02-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}