{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T02:00:44Z","timestamp":1785117644804,"version":"3.55.0"},"reference-count":68,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and emerging dual incretin therapies have demonstrated substantial effects on weight reduction and metabolic improvement, with growing evidence supporting favorable cardiovascular outcomes. This narrative review provides a focused overview of key cardiovascular outcomes trials (CVOTs) and HFpEF-oriented clinical studies evaluating GLP-1 RA and dual incretin therapies in patients living with obesity, including completed and ongoing investigations. We summarize trial characteristics, critically appraise their outcomes, and briefly discuss mechanistic pathways potentially linking incretin-based therapies to cardiovascular and HFpEF-related benefits. Because available data derive from heterogeneous study designs, we explicitly distinguish evidence from type 2 diabetes cardiovascular outcomes trials, obesity-without-diabetes cardiovascular outcomes trials, HFpEF-specific randomized trials, mechanistic substudies, ongoing trials, and real-world observational analyses. We also situate incretin-based therapies within contemporary obesity, diabetes, cardiovascular, and HFpEF guideline-directed care. Finally, we identify current knowledge gaps, future research priorities, and innovative approaches needed to refine personalized therapeutic strategies and optimize patient-centered outcomes in obesity-associated HFpEF.<\/jats:p>","DOI":"10.3390\/medicina62081446","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T01:26:23Z","timestamp":1785115583000},"page":"1446","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glucagon-like Peptide-1 Receptor Agonists and Dual Incretin Therapies Across HFpEF and Cardiovascular Outcomes Trials in Patients with Obesity"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7848-6600","authenticated-orcid":false,"given":"Andrej","family":"Belan\u010di\u0107","sequence":"first","affiliation":[{"name":"Department of Basic and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0287-4735","authenticated-orcid":false,"given":"Sanja","family":"Klobu\u010dar","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolic Diseases, Clinical Hospital Centre Rijeka, 51000 Rijeka, Croatia"},{"name":"Department of Internal Medicine, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0379-5235","authenticated-orcid":false,"given":"Kristina","family":"Skro\u010de","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea","family":"Ciudin","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Group, VHIR, Endocrinology Department, Vall d\u2019Hebron University Hospital, Autonomus University of Barcelona, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4878-8146","authenticated-orcid":false,"given":"Josip An\u0111elo","family":"Borovac","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, University Hospital of Split, 21000 Split, Croatia"},{"name":"Department of Pathophysiology, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2026). 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