{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:13:54Z","timestamp":1793726034960,"version":"4.6.1"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["T32 HL007576"],"award-info":[{"award-number":["T32 HL007576"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Kidney Foundation","award":["REACH (Research and Advancement in Cardiorenal Health) Award, A Joint Effort from NKF, Bayer and Women in Nephrology"],"award-info":[{"award-number":["REACH (Research and Advancement in Cardiorenal Health) Award, A Joint Effort from NKF, Bayer and Women in Nephrology"]}]},{"name":"Bayer","award":["REACH (Research and Advancement in Cardiorenal Health) Award, A Joint Effort from NKF, Bayer and Women in Nephrology"],"award-info":[{"award-number":["REACH (Research and Advancement in Cardiorenal Health) Award, A Joint Effort from NKF, Bayer and Women in Nephrology"]}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01 DK128640"],"award-info":[{"award-number":["R01 DK128640"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["R01 AG074592"],"award-info":[{"award-number":["R01 AG074592"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["T35 DK103596"],"award-info":[{"award-number":["T35 DK103596"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Office of Rural Health"},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"crossref","award":["UL1TR002538"],"award-info":[{"award-number":["UL1TR002538"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"crossref","award":["UM1TR004409"],"award-info":[{"award-number":["UM1TR004409"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>In veterans with type 2 diabetes and low kidney failure risk, sodium-glucose cotransporter 2 inhibitors (SGLT2is) were more kidney protective while glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were more cardioprotective.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>For cardiovascular-kidney-metabolic outcomes, GLP-1 RAs were more protective at moderate kidney failure risk and SGLT2is were more protective at high kidney failure risk.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The kidney failure risk equation might be a clinically useful tool to guide therapy in type 2 diabetes.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Head-to-head comparisons of non-exendin glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) on kidney failure or cardiovascular-kidney-metabolic (CKM) composite end points are lacking. Whether kidney failure risk modifies the comparative effectiveness of GLP-1 RA versus SGLT2i is clinically relevant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We defined a national veterans cohort with type 2 diabetes who initiated an SGLT2i, non-exendin GLP-1 RA, or insulin glargine between January 1, 2018, and December 31, 2021. After applying inverse probability of treatment weighting to balance baseline characteristics, outcomes were compared across new-user groups through March 31, 2023. Outcomes included kidney failure (stage 5 CKD or long-term KRT), major adverse cardiovascular events (MACEs: heart failure, myocardial infarction, or stroke), CKM composite (kidney failure or MACE), all-cause death, and composites of outcomes with death. We tested for effect modification by the kidney failure risk equation (KFRE) score on comparative pairwise drug effectiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Out of 160,428 veterans, 53%, 14%, and 34% were new users of SGLT2i, GLP-1 RA, and insulin glargine, respectively. Relative to GLP-1 RA new-users, SGLT2i new-users had similar mortality risk, a trend toward lower kidney failure risk (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.74 to 1.06), but higher risk of MACE (HR, 1.14; 95% CI, 1.09 to 1.20) and CKM composite (HR, 1.13; 95% CI, 1.08 to 1.19). The effect of SGLT2i versus GLP-1 RA differed significantly between moderate-risk (2%\u20136%) and high-risk (\u22656%) KFRE subgroups for all outcomes except all-cause death. In those with moderate-risk KFRE, GLP-1 RA seemed more protective for kidney failure, MACE, and CKM composite, while SGLT2i appeared more protective in those with high-risk KFRE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Compared with GLP-1 RA, SGLT2i had comparable risks of mortality, perhaps a lower risk of kidney failure, but modestly higher risk of cardiovascular events in the entire cohort. However, GLP-1 RA were more beneficial in those with moderate kidney failure risk and SGLT2i more beneficial in those with high kidney failure risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Podcast<\/jats:title>\n                    <jats:p>This article contains a podcast at https:\/\/dts.podtrac.com\/redirect.mp3\/\/www.asn-online.org\/media\/podcast\/JASN\/2026_07_29_KTS_July2026.mp3<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.0000001016","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T17:00:19Z","timestamp":1768323619000},"page":"1733-1747","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":4,"title":["Comparative Effectiveness of SGLT2 Inhibitor and GLP-1 Receptor Agonist on Kidney and Cardiovascular Outcomes by Kidney Failure Risk"],"prefix":"10.1681","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7328-3732","authenticated-orcid":false,"given":"Sydney E.","family":"Hartsell","sequence":"first","affiliation":[{"name":"Cardiovascular, Renal and Metabolism Center, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah"},{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah"},{"name":"George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah"},{"name":"Nora Eccles Harrison Cardiovascular Research and Training Institute, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4971-8430","authenticated-orcid":false,"given":"Guo","family":"Wei","sequence":"additional","affiliation":[{"name":"Cardiovascular, Renal and Metabolism Center, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah"},{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah"},{"name":"George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7221-8557","authenticated-orcid":false,"given":"Ravinder","family":"Singh","sequence":"additional","affiliation":[{"name":"Cardiovascular, Renal and Metabolism Center, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah"},{"name":"George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah"},{"name":"Division of Biostatistics, Department of Population Health Sciences, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4773-2781","authenticated-orcid":false,"given":"Michael","family":"Throolin","sequence":"additional","affiliation":[{"name":"Cardiovascular, Renal and Metabolism Center, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah"},{"name":"George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah"},{"name":"Division of Biostatistics, Department of Population Health Sciences, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"McKenna R.","family":"Nevers","sequence":"additional","affiliation":[{"name":"Cardiovascular, Renal and Metabolism Center, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah"},{"name":"George E. 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