{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:19:39Z","timestamp":1788326379633,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004895","name":"European Social Fund Plus","doi-asserted-by":"publisher","award":["EFOP\u20103.6.2\u201016\u20102017\u201000009"],"award-info":[{"award-number":["EFOP\u20103.6.2\u201016\u20102017\u201000009"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017591","name":"Magyar Diabetes T\u00e1rsas\u00e1g","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017591","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Incretin\u2010based pharmacotherapy was initially developed to improve glucose\u2010dependent insulin secretion and glycaemic control in type 2 diabetes, but its clinical interpretation has expanded substantially with cardiovascular outcome trials, kidney outcome data, obesity studies and next\u2010generation polyagonist development. This narrative clinical review uses structured literature identification and outcome\u2010stratified synthesis to evaluate incretin\u2010based therapies as cardiometabolic interventions across diabetes, obesity, cardiovascular disease and chronic kidney disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>The available evidence was interpreted according to therapeutic class, clinical domain, outcome maturity and safety boundaries, integrating clinical outcome evidence with receptor\u2010network pharmacology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Selected GLP\u20101 receptor agonists are supported by hard cardiovascular and renal outcome data, whereas several dual, triple, amylin\u2010linked and oral small\u2010molecule strategies are currently supported mainly by glycaemic, weight\u2010loss, metabolic or early translational endpoints. This distinction is clinically important because treatment positioning should depend on patient phenotype, outcome maturity and safety boundaries rather than mechanistic plausibility alone. In patients with type 2 diabetes and established atherosclerotic cardiovascular disease, GLP\u20101 receptor agonists with proven cardiovascular outcome benefit should be prioritised when atherosclerotic risk reduction is a major treatment goal. In type 2 diabetes with chronic kidney disease, semaglutide has dedicated kidney outcome evidence. In obesity with cardiometabolic risk, high\u2010magnitude and sustained weight reduction has become a clinically relevant therapeutic target. Receptor\u2010network pharmacology, including GLP\u20101, GIP, glucagon and amylin receptor signalling, provides a useful explanatory framework for heterogeneous efficacy, tolerability and tissue\u2010level effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>However, clinical use remains bounded by gastrointestinal tolerability, lean\u2010mass preservation, treatment durability, discontinuation effects and long\u2010term safety. This review therefore proposes phenotype\u2010based clinical positioning rather than a prescriptive treatment algorithm.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71277","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T04:28:45Z","timestamp":1788323325000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Incretin\u2010Based Therapies as Cardiometabolic Interventions: Outcome Hierarchy, Receptor\u2010Network Pharmacology and Phenotype\u2010Based Clinical Positioning"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6657-7579","authenticated-orcid":false,"given":"Ferenc","family":"Sztanek","sequence":"first","affiliation":[{"name":"Division of Metabolism, Department of Internal Medicine, Faculty of Medicine University of Debrecen  Debrecen 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