{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:50:23Z","timestamp":1792698623006,"version":"4.5.0"},"reference-count":42,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2026,1,20]]},"abstract":"<jats:sec id=\"ab-joi250095-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>There is uncertainty about the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in participants with chronic kidney disease, with guidelines offering different strengths of recommendation based on diabetes status and urine albumin to creatinine ratio (UACR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-joi250095-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the relative and absolute effects of SGLT2 inhibitor use across efficacy and serious safety outcomes in participants stratified by diabetes status and UACR (\u2265200 mg\/g or &amp;amp;lt;200 mg\/g).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-joi250095-6\">\n                    <jats:title>Data Sources and Study Selection<\/jats:title>\n                    <jats:p>Included 8 randomized clinical trials that studied an SGLT2 inhibitor with a label indication for use in kidney disease and recorded longitudinal kidney outcomes and baseline data on albuminuria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-joi250095-7\">\n                    <jats:title>Data Extraction and Synthesis<\/jats:title>\n                    <jats:p>Data were combined using inverse variance\u2013weighted meta-analysis; group-specific absolute effects were estimated by applying relevant relative risks to the event rates of the placebo groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-joi250095-8\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Assessed the effects of SGLT2 inhibitor use on clinical efficacy and safety outcomes. Heterogeneity by baseline level of UACR was assessed separately by diabetes status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-joi250095-9\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 58\u202f816 participants (mean age, 64 [SD, 10] years; 35% were female; 48\u202f946 with diabetes and 9870 without diabetes) were included from trials comparing an SGLT2 inhibitor vs placebo. Allocation to an SGLT2 inhibitor produced a lower rate of kidney disease progression (33 vs 48 for placebo per 1000 patient-years; hazard ratio [HR], 0.65 [95% CI, 0.60-0.70] in those with diabetes and 32 vs 46 per 1000; HR, 0.74 [95% CI, 0.63-0.85] in those without diabetes), a lower rate of acute kidney injury (14 vs 18 per 1000 [HR, 0.77; 95% CI, 0.69-0.87] with diabetes and 13 vs 18 per 1000 [HR, 0.72; 95% CI, 0.56-0.92] without diabetes), a lower rate of any hospitalization (202 vs 231 per 1000 [HR, 0.90; 95% CI, 0.87-0.92] with diabetes and 203 vs 237 per 1000 [HR, 0.89; 95% CI, 0.83-0.95] without diabetes), and a lower rate of any death (42 vs 47 per 1000 [HR, 0.86; 95% CI, 0.80-0.91] with diabetes and 42 vs 48 per 1000 [HR, 0.91; 95% CI, 0.78-1.05] without diabetes). Diabetes-specific HRs were similar in participants (with a UACR \u2265200 mg\/g vs with a UACR &amp;amp;lt;200 mg\/g) considered separately. Higher absolute risk at a UACR of 200 mg\/g or greater meant larger estimated absolute benefits on kidney disease progression were evident in this subgroup. Clear absolute benefits were evident for other efficacy outcomes, and particularly hospitalization, in participants with a UACR less than 200 mg\/g. Net absolute benefits remained in the analyses of non\u2013heart failure populations and when estimated glomerular filtration rate was less than 60 mL\/min\/1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-joi250095-10\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>Within the studied participants, there were clear absolute benefits of SGLT2 inhibitors on kidney, hospitalization, and mortality outcomes irrespective of diabetes status and level of UACR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jama.2025.20835","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T18:30:20Z","timestamp":1762540220000},"page":"220","source":"Crossref","is-referenced-by-count":31,"title":["Effects of Sodium Glucose Cotransporter 2 Inhibitors by Diabetes Status and Level of Albuminuria"],"prefix":"10.1001","volume":"335","author":[{"given":"Natalie","family":"Staplin","sequence":"first","affiliation":[{"name":"Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, England"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair J.","family":"Roddick","sequence":"additional","affiliation":[{"name":"Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, England"},{"name":"Oxford Kidney Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, England"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendon L.","family":"Neuen","sequence":"additional","affiliation":[{"name":"George Institute for Global Health, University of New South Wales, Sydney, Australia"},{"name":"Department of Renal Medicine, Royal North Shore Hospital, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[{"name":"Department of Cardiology, German Heart Center Charit\u00e9, Berlin, Germany"},{"name":"Institute of Health Center for Regenerative Therapies, German Centre for Cardiovascular Research partner site Berlin, Charit\u00e9 Universit\u00e4tsmedizin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak L.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Mount Sinai Heart, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javed","family":"Butler","sequence":"additional","affiliation":[{"name":"Baylor Scott and White Research Institute, Temple, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Z.","family":"Cherney","sequence":"additional","affiliation":[{"name":"Toronto General Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kieran F.","family":"Docherty","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Fletcher","sequence":"additional","affiliation":[{"name":"George Institute for Global Health, University of New South Wales, Sydney, Australia"},{"name":"Department of Public Health and Primary Care, British Heart Foundation Cardiovascular Epidemiology Unit, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, England"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvio E.","family":"Inzucchi","sequence":"additional","affiliation":[{"name":"School of Medicine, Yale University, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meg","family":"Jardine","sequence":"additional","affiliation":[{"name":"NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth W.","family":"Mahaffey","sequence":"additional","affiliation":[{"name":"Stanford Center for Clinical Research, Department of Medicine, Stanford University, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren K.","family":"McGuire","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J. 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