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Semaglutide, a selective agonist of the glucagon-like peptide-1 (GLP-1) receptor, has consolidated its clinical role through an efficacy profile that combines marked improvement in glycaemic control, substantial body weight reduction, and well-established cardiovascular and renal benefits. Tirzepatide, the first dual agonist of the glucose-dependent insulinotropic polypeptide and GLP-1 receptors, has introduced a new generation of incretin-based agents, characterized by a superior impact on weight loss and insulin sensitivity, with a potential expansion of therapeutic indications. Although both molecules share a remarkable ability to reduce body weight and HbA1c levels, they differ in their mechanisms of action, current therapeutic indications, and the robustness of available evidence on cardiovascular outcomes. Their integration into clinical practice therefore requires a personalized approach that balances metabolic efficacy, safety, and individual patient risk profiles. Within this context, the incretin revolution offers new perspectives for cardio\u2013reno\u2013metabolic prevention.<\/jats:p>","DOI":"10.1093\/eurheartjsupp\/suag028","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T12:21:23Z","timestamp":1771849283000},"page":"v57-v61","source":"Crossref","is-referenced-by-count":0,"title":["Tirzepatide and semaglutide: different twins?"],"prefix":"10.1093","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4435-1235","authenticated-orcid":false,"given":"Arturo","family":"Cesaro","sequence":"first","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u2018Luigi Vanvitelli\u2019 , Via L. 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