{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T10:01:39Z","timestamp":1780653699163,"version":"3.54.1"},"reference-count":39,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Internal Medicine Department, Regional University Hospital of Malaga"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Bacground\/Objectives: There is limited evidence on the role of glucagon-like peptide-1 receptor agonists in heart failure. We aimed to analyze the clinical efficacy of oral semaglutide in terms of health status and change in body weight in patients with heart failure with reduced ejection fraction, type 2 diabetes, and obesity. Methods: This observational, retrospective, real-world study included patients treated with oral semaglutide (Oral-Sema Group) and without glucagon-like peptide-1 receptor agonists (Control Group). The primary outcome was heart failure status, defined as a \u22655 point difference in the Kansas City Cardiomyopathy Questionnaire total symptom score, and change in body weight at 24 months. Results: After 1:1 propensity score matching, 162 patients were included in each group (mean age 71.0 years, mean body mass index 32.1, 52.9% females). Patients in the Oral-Sema Group were more likely to have improvement in heart failure health status from baseline to 24 months (OR: 2.45; 95%CI: 1.25\u20133.65; p = 0.012). The mean change in body weight was \u22128.0 \u00b1 2.1 kg in patients with oral semaglutide and \u22121.9 \u00b1 1.0 kg in control patients (p &lt; 0.01). After treatment, there were negative correlations between the Kansas City Cardiomyopathy Questionnaire total symptom score and body weight (r = \u22120.558, p &lt; 0.01) and glycated hemoglobin (r = \u22120.491, p = 0.017). It had good tolerability and safety. Conclusions: Oral semaglutide was associated with an improvement in heart failure health status and weight loss in patients with heart failure with reduced ejection fraction, type 2 diabetes, and obesity. Further research on glucagon-like peptide-1 receptor agonists in heart failure with reduced ejection fraction is needed.<\/jats:p>","DOI":"10.3390\/ph19060894","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T08:43:04Z","timestamp":1780648984000},"page":"894","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Effectiveness and Safety of Oral Semaglutide in a Real-World Cohort of Patients with Heart Failure with Reduced Ejection Fraction, Type 2 Diabetes and Obesity: A Propensity Score-Matched Analysis"],"prefix":"10.3390","volume":"19","author":[{"given":"Alicia","family":"Trenas-Calero","sequence":"first","affiliation":[{"name":"IBIMA Plataforma BIONAND, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga, 29590 M\u00e1laga, Spain"},{"name":"Servicio de Medicina Interna, Hospital Regional Universitario de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Prieto-La\u00edn","sequence":"additional","affiliation":[{"name":"IBIMA Plataforma BIONAND, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga, 29590 M\u00e1laga, Spain"},{"name":"Servicio de Medicina Interna, Hospital Regional Universitario de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9907-8817","authenticated-orcid":false,"given":"Miguel A.","family":"P\u00e9rez-Velasco","sequence":"additional","affiliation":[{"name":"IBIMA Plataforma BIONAND, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga, 29590 M\u00e1laga, Spain"},{"name":"Servicio de Medicina Interna, Hospital Regional Universitario de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Padilla-Leiva","sequence":"additional","affiliation":[{"name":"IBIMA Plataforma BIONAND, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga, 29590 M\u00e1laga, Spain"},{"name":"Servicio de Medicina Interna, Hospital Regional Universitario de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"P\u00e9rez-Ruiz","sequence":"additional","affiliation":[{"name":"IBIMA Plataforma BIONAND, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga, 29590 M\u00e1laga, Spain"},{"name":"Servicio de Cardiolog\u00eda, Hospital Regional Universitario de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1tima I.","family":"Ru\u00edz-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"IBIMA Plataforma BIONAND, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga, 29590 M\u00e1laga, Spain"},{"name":"Servicio de Cardiolog\u00eda, Hospital Regional Universitario de M\u00e1laga, 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9909-3555","authenticated-orcid":false,"given":"Ricardo","family":"G\u00f3mez-Huelgas","sequence":"additional","affiliation":[{"name":"IBIMA Plataforma BIONAND, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga, 29590 M\u00e1laga, Spain"},{"name":"Servicio de Medicina Interna, Hospital Regional Universitario de M\u00e1laga, 29010 M\u00e1laga, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Departamento de Medicina y Dermatolog\u00eda, Facultad de Medicina, Universidad de M\u00e1laga (UMA), 29010 M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0238-0890","authenticated-orcid":false,"given":"Mar\u00eda-Rosa","family":"Bernal-L\u00f3pez","sequence":"additional","affiliation":[{"name":"IBIMA Plataforma BIONAND, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga, 29590 M\u00e1laga, Spain"},{"name":"Servicio de Medicina Interna, Hospital Regional Universitario de M\u00e1laga, 29010 M\u00e1laga, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9512-8274","authenticated-orcid":false,"given":"Luis M.","family":"P\u00e9rez-Belmonte","sequence":"additional","affiliation":[{"name":"IBIMA Plataforma BIONAND, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga, 29590 M\u00e1laga, Spain"},{"name":"Servicio de Medicina Interna, Hospital Regional Universitario de M\u00e1laga, 29010 M\u00e1laga, Spain"},{"name":"Departamento de Medicina y Dermatolog\u00eda, Facultad de Medicina, Universidad de M\u00e1laga (UMA), 29010 M\u00e1laga, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.2337\/dc17-0697","article-title":"Prognostic Impact of Diabetes on Long-term Survival Outcomes in Patients with Heart Failure: A Meta-analysis","volume":"40","author":"Dauriz","year":"2017","journal-title":"Diabetes Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ejim.2018.04.005","article-title":"National trends in diabetes mellitus hospitalisation in Spain 1997\u20132010: Analysis of over 5.4 millions of admissions","volume":"60","year":"2019","journal-title":"Eur. J. Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhao, L., Zhang, J., Liu, W., Dai, C., and Li, A. (2025). GV effects of diabetes mellitus on clinical outcomes of patients with acute heart failure: A systematic review and meta-analysis. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0338653"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ejim.2021.11.008","article-title":"Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors for cardiovascular and renal protection: A treatment approach far beyond their glucose-lowering effect","volume":"96","year":"2022","journal-title":"Eur. J. Intern. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Professional Practice Committee for Diabetes (2026). 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2026. Diabetes Care, 49, S216\u2013S245.","DOI":"10.2337\/dc26-S010"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.rce.2020.06.005","article-title":"Medical treatment of type 2 diabetes mellitus: Recommendations of the Diabetes, Obesity and Nutrition Group of the Spanish Society of Internal Medicine","volume":"221","author":"Ena","year":"2021","journal-title":"Rev. Clin. Esp."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1056\/NEJMoa1911303","article-title":"Dapagliflozin in patients with heart failure and reduced ejection fraction","volume":"381","author":"McMurray","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1056\/NEJMoa2022190","article-title":"Cardiovascular and renal outcomes with empagliflozin in heart failure","volume":"383","author":"Packer","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/S2213-8587(19)30249-9","article-title":"Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: A systematic review and meta-analysis of cardiovascular outcome trials","volume":"7","author":"Kristensen","year":"2019","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/S0140-6736(24)01643-X","article-title":"Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: A pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials","volume":"404","author":"Kosiborod","year":"2024","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1056\/NEJMoa2313917","article-title":"Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes","volume":"390","author":"Kosiborod","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1056\/NEJMoa2306963","article-title":"Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity","volume":"389","author":"Kosiborod","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1056\/NEJMoa2307563","article-title":"Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes","volume":"389","author":"Lincoff","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1056\/NEJMoa2403347","article-title":"Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes","volume":"391","author":"Perkovic","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1056\/NEJMoa2410027","article-title":"Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity","volume":"392","author":"Packer","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1056\/NEJMoa1901118","article-title":"Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes","volume":"381","author":"Husain","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/ejhf.2333","article-title":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"24","author":"McDonagh","year":"2022","journal-title":"Eur. J. Heart Fail."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1056\/NEJMoa2501006","article-title":"Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes","volume":"392","author":"McGuire","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1001\/jamainternmed.2025.7774","article-title":"Oral Semaglutide and Heart Failure Outcomes in Persons with Type 2 Diabetes: A Secondary Analysis of the SOUL Randomized Clinical Trial","volume":"186","author":"Rasmussen","year":"2026","journal-title":"JAMA Intern. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"106378","DOI":"10.1016\/j.ejim.2025.06.007","article-title":"Efficacy and safety of once-daily oral semaglutide in patients with heart failure with preserved ejection fraction, type 2 diabetes and obesity: A real-world study","volume":"139","author":"Trenas","year":"2025","journal-title":"Eur. J. Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"173","DOI":"10.2337\/dbi20-0049","article-title":"Cardiovascular Effects of Incretin-Based Therapies: Integrating Mechanisms with Cardiovascular Outcome Trials","volume":"71","author":"Ussher","year":"2022","journal-title":"Diabetes"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1161\/CIRCULATIONAHA.117.028136","article-title":"Cardiovascular Actions and Clinical Outcomes with Glucagon-Like Peptide-1 Receptor Agonists and Dipeptidyl Peptidase-4 Inhibitors","volume":"136","author":"Nauck","year":"2017","journal-title":"Circulation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e70","DOI":"10.1093\/cvr\/cvy124","article-title":"Glucagon-like peptide-1 receptor agonists and cardiovascular disease: From LEADER to EXSCEL","volume":"114","author":"Torekov","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Greco, E.V., Russo, G., Giandalia, A., Viazzi, F., Pontremoli, R., and De Cosmo, S. (2019). GLP-1 Receptor Agonists and Kidney Protection. Medicina, 55.","DOI":"10.3390\/medicina55060233"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1016\/S1262-3636(17)30069-1","article-title":"The potential and pitfalls of GLP-1 receptor agonists for renal protection in type 2 diabetes","volume":"43","author":"Thomas","year":"2017","journal-title":"Diabetes Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"891","DOI":"10.7150\/ijms.19854","article-title":"Expression of epicardial adipose tissue thermogenic genes in patients with reduced and preserved ejection fraction heart failure","volume":"14","year":"2017","journal-title":"Int. J. Med. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.cardfail.2025.06.013","article-title":"The Continuum of Prevention and Heart Failure in Cardiovascular Medicine: A Joint Scientific Statement from the Heart Failure Society of America and The American Society for Preventive Cardiology","volume":"32","author":"Lala","year":"2026","journal-title":"J. Card. Fail."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1016\/S0140-6736(25)01393-5","article-title":"Prioritising the primary prevention of heart failure","volume":"406","author":"Khan","year":"2025","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1016\/j.jacc.2022.02.025","article-title":"Nutrition Assessment and Dietary Interventions in Heart Failure: JACC Review Topic of the Week","volume":"79","author":"Driggin","year":"2022","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.pcad.2020.09.005","article-title":"Implications of obesity across the heart failure continuum","volume":"63","author":"Elagizi","year":"2020","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1016\/j.jchf.2024.06.006","article-title":"Obesity and Weight Loss Strategies for Patients with Heart Failure","volume":"12","author":"Vest","year":"2024","journal-title":"JACC Heart Fail."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S2213-8587(24)00155-4","article-title":"Efficacy and safety of SGLT2 inhibitors with and without glucagon-like peptide 1 receptor agonists: A SMART-C collaborative meta-analysis of randomised controlled trials","volume":"12","author":"Apperloo","year":"2024","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/eurheartj\/ehad703","article-title":"Going green in cardiology","volume":"45","author":"Khanji","year":"2024","journal-title":"Eur. Heart J."},{"key":"ref_34","first-page":"209","article-title":"The Impact of Obesity in Heart Failure","volume":"40","author":"Carbone","year":"2022","journal-title":"Cardiol. Clin."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Cuesta-Vargas, A.I., Fuentes-Abolafio, I.J., Garc\u00eda-Conejo, C., D\u00edaz-Balboa, E., Trinidad-Fern\u00e1ndez, M., Guti\u00e9rrez-S\u00e1nchez, D., Escriche-Escuder, A., Cobos-Palacios, L., L\u00f3pez-Sampalo, A., and P\u00e9rez-Ru\u00edz, J.M. (2023). Effectiveness of a cardiac rehabilitation program on biomechanical, imaging, and physiological biomarkers in elderly patients with heart failure with preserved ejection fraction (HFpEF): FUNNEL + study protocol. BMC Cardiovasc. Disord., 23.","DOI":"10.1186\/s12872-023-03555-7"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/eurjcn\/zvad027","article-title":"Kinematic parameters related to functional capacity, fatigue, and breathlessness during the 6-min walk test in older adults with heart failure with preserved ejection fraction","volume":"23","author":"Ricci","year":"2024","journal-title":"Eur. J. Cardiovasc. Nurs."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Professional Practice Committee (2022). 2. Classification and diagnosis of diabetes: Standards of medical care in diabetes-2022. Diabetes Care, 45, S17\u2013S38.","DOI":"10.2337\/dc22-S002"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.recesp.2010.10.003","article-title":"Validation of the Spanish version of the Kansas city cardiomyopathy questionnaire","volume":"64","author":"Garin","year":"2011","journal-title":"Rev. Esp. Cardiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1093\/eurjhf\/hft128","article-title":"The Chronic Kidney Disease Epidemiology Collaboration equation outperforms the Modification of Diet in Renal Disease equation for estimating glomerular filtration rate in chronic systolic heart failure","volume":"16","author":"Valente","year":"2014","journal-title":"Eur. J. Heart Fail."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/6\/894\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T09:07:11Z","timestamp":1780650431000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/6\/894"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,5]]},"references-count":39,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ph19060894"],"URL":"https:\/\/doi.org\/10.3390\/ph19060894","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,5]]}}}