{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:04:50Z","timestamp":1786122290678,"version":"build-2736575974"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Chronic kidney disease (CKD) confers substantial cardiovascular and renal morbidity. GLP\u20101 receptor agonists (GLP\u20101 RAs) have demonstrated cardiorenal protection across major randomised trials, culminating in the landmark FLOW trial. No prior systematic review has simultaneously synthesised cardiorenal outcomes in a CKD\u2010restricted population, executed a network meta\u2010analysis for agent\u2010level comparisons, or assessed whether SGLT2 inhibitor background therapy modifies treatment effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      MEDLINE, Embase, Cochrane CENTRAL, and Web of Science were searched through March 2025. Eligible RCTs enrolled adults with CKD (eGFR &lt;\u200960\u2009mL\/min\/1.73\u2009m\n                      <jats:sup>2<\/jats:sup>\n                      or UACR \u2265\u200930\u2009mg\/g) comparing GLP\u20101 RAs versus placebo for \u2265\u200926\u2009weeks. Primary outcomes were 3\u2010point MACE and a KDIGO\u2010harmonised composite kidney endpoint. Random\u2010effects pairwise meta\u2010analyses and a frequentist NMA were performed. GRADE certainty was assigned to all outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirteen RCTs (97\u2009428 participants; 31\u2009846 with confirmed CKD) were included. GLP\u20101 RAs reduced MACE by 16% (HR 0.84, 95% CI 0.79\u20130.89; high certainty) and the composite kidney endpoint by 21% (HR 0.79, 95% CI 0.73\u20130.86; high certainty). Kidney failure risk was reduced by 28% (HR 0.72); UACR decreased by 26%. Benefits were consistent irrespective of SGLT2 inhibitor background use (interaction\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.41). Semaglutide ranked highest in the NMA (SUCRA 78.4%). No excess acute kidney injury risk was observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>GLP\u20101 RAs provide clinically meaningful cardiorenal protection in CKD, additive to SGLT2 inhibitor benefits. In exploratory network meta\u2010analysis, semaglutide subcutaneous achieved the highest SUCRA ranking for kidney composite outcomes; the direct semaglutide evidence is rated high certainty by GRADE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71031","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T01:39:09Z","timestamp":1782265149000},"page":"8337-8346","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and Safety of\n                    <scp>GLP<\/scp>\n                    \u20101 Receptor Agonists on Combined Cardiovascular and Renal Outcomes in Patients With Chronic Kidney Disease: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1111","volume":"28","author":[{"given":"Rashpinder","family":"Kaur","sequence":"first","affiliation":[{"name":"General Medicine and Care of the Elderly, Aneurin Bevan University Health Board  Newport UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4705-0818","authenticated-orcid":false,"given":"Avtar","family":"Singh","sequence":"additional","affiliation":[{"name":"General Medicine and Care of the Elderly, Aneurin Bevan University Health Board  Newport UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"issue":"3","key":"e_1_2_11_2_1","first-page":"S117","article-title":"KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease","volume":"105","author":"Kidney Disease: Improving Global Outcomes (KDIGO)","year":"2024","journal-title":"Kidney International"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204233"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2403347"},{"issue":"6","key":"e_1_2_11_5_1","first-page":"669","article-title":"Glucagon\u2010Like Peptide\u20101 Receptor Agonists: New Evidence of Kidney and Cardiovascular Protection","volume":"84","author":"Taal M. W.","year":"2024","journal-title":"American Journal of Kidney Diseases"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(21)00203-5"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(24)00271-7"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2024.11.013"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4898"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1603827"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1607141"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31149-3"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32261-X"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2108269"},{"issue":"4","key":"e_1_2_11_16_1","first-page":"323","article-title":"Oral Semaglutide and Cardiovascular Outcomes in High\u2010Risk Type 2 Diabetes","volume":"392","author":"McGuire D. K.","year":"2025","journal-title":"New England Journal of Medicine"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1901118"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(19)30192-5"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1612917"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509225"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(18)30104-9"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2307563"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc25-1673"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.055459"},{"issue":"18","key":"e_1_2_11_25_1","first-page":"1775","article-title":"Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease","volume":"84","author":"Pratley R. E.","year":"2024","journal-title":"Journal of the American College of Cardiology"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.124.071689"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2025.109178"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2025.112379"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnha.2025.100632"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apjo.2025.100245"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.71031","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.71031","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.71031","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T08:51:32Z","timestamp":1786092692000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/10.1111\/dom.71031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":29,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/dom.71031"],"URL":"https:\/\/doi.org\/10.1111\/dom.71031","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/DOM.71031\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.71031\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.71031\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.71031\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.71031\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.71031\/v1\/review1","asserted-by":"object"}]},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,23]]},"assertion":[{"value":"2026-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}