{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:36:47Z","timestamp":1790012207018,"version":"4.0.1"},"reference-count":260,"publisher":"The Endocrine Society","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cardiovascular\u2013kidney\u2013metabolic (CKM) syndrome represents an intricate and interdependent nexus among metabolic risk factors, such as diabetes and obesity, chronic kidney disease (CKD), and cardiovascular disease (CVD), collectively exerting a profound impact on global morbidity and mortality. The rising prevalence of type 2 diabetes (T2D) underscores the urgent need for therapeutic strategies that transcend glycemic control to target the intricate pathophysiology underlying these conditions. This review examines the expanding role of novel antidiabetic drug classes, including sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dual or triple-incretin agonists, across the CKM continuum. These agents have demonstrated significant benefits in reducing major adverse cardiovascular events (MACEs), attenuating CKD progression, and enhancing metabolic health, independent of their glucose-lowering properties. Across the CKM continuum, we prioritize weight-centric incretin therapy (GLP-1RAs or dual incretins) in stage 0-1 (obesity\/prediabetes), SGLT2 inhibitors first for albuminuric CKD and\/or heart failure risk in stage 2 (with early addition of GLP-1RAs when CVD\/obesity predominates), and layered combination therapy in stage 3, typically SGLT2 inhibitor + GLP-1RA\/dual incretin (\u00b1 finerenone for persistent albuminuria), to maximize cardiovascular and kidney protection. By synthesizing evidence from pivotal clinical trials, evaluating emerging combination therapies, and delineating the evolving treatment paradigm, this review aims to provide a comprehensive perspective on how these antidiabetic therapies influence CKM syndrome management. As research advances, an integrated, multifaceted approach to diabetes care leveraging these agents may lead to substantial improvements in cardiovascular, kidney, and metabolic outcomes.<\/jats:p>","DOI":"10.1210\/endrev\/bnag022","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T15:09:01Z","timestamp":1783955341000},"source":"Crossref","is-referenced-by-count":3,"title":["Newer and novel antidiabetic drug classes across the cardiovascular\u2013kidney\u2013metabolic continuum"],"prefix":"10.1210","author":[{"given":"Konstantinos","family":"Stefanakis","sequence":"first","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA 02215 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paschalis","family":"Karakasis","sequence":"additional","affiliation":[{"name":"Second Department of Cardiology, General Hospital \u201cHippokration\u201d, Aristotle University of Thessaloniki , Thessaloniki 54642 ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Vasdeki","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital , Thessaloniki 54636 ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djordje S","family":"Popovic","sequence":"additional","affiliation":[{"name":"Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Centre of Vojvodina , Novi Sad 21137 ,","place":["Serbia"]},{"name":"Medical Faculty, University of Novi Sad , Novi Sad 21000 ,","place":["Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6899-684X","authenticated-orcid":false,"given":"Dimitrios","family":"Patoulias","sequence":"additional","affiliation":[{"name":"Second Propedeutic Department of Internal Medicine, General Hospital \u201cHippokration\u201d, Aristotle University of Thessaloniki , Thessaloniki 54642 ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9549-8504","authenticated-orcid":false,"given":"Manfredi","family":"Rizzo","sequence":"additional","affiliation":[{"name":"College of Medicine, Ras Al Khaimah Medical and Health Sciences University (RAKMHSU) , RAK 11172 ,","place":["United Arab Emirates"]},{"name":"School of Medicine, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), University of Palermo , Palermo 90133 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