{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:52:40Z","timestamp":1791903160519,"version":"4.3.4"},"reference-count":28,"publisher":"The Endocrine Society","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated clinical benefits in heart failure with preserved ejection fraction (HFpEF) and obesity. However, its effects on cardiorenal biomarkers and functional capacity have not been comprehensively synthesized. We hypothesized that tirzepatide produces significant reductions in cardiorenal biomarkers and improvements in functional capacity compared to placebo or standard of care.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This systematic review and meta-analysis (PROSPERO: CRD42026137255) searched PubMed, Embase, CENTRAL, Web of Science, and Scopus from inception to April 17, 2026, without restrictions. Randomized controlled trials and prospective observational studies reporting NT-proBNP, high-sensitivity C-reactive protein (hsCRP), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), 6-minute walk test (6\u2005MWT), or renal outcomes with tirzepatide vs placebo or standard of care were included. Data were pooled using random-effects models with Hartung\u2013Knapp\u2013Sidik\u2013Jonkman adjustment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seven studies (5 RCTs, 2 observational; 5406 participants) were included. Tirzepatide significantly reduced hsCRP by 34.3% (95% CI: \u221238.4% to \u221230.1%; P &amp;lt; .0001; I2 = 0.0%; 6 studies) and NT-proBNP by 17.6% (95% CI: \u221226.7% to \u22128.5%; P = .0001; I2 = 58.1%; 3 studies). In the SUMMIT trial, KCCQ-CSS improved by 5.1 points (P &amp;lt; .001) and 6\u2005MWT by 15.8 m (P = .004). Single-trial data demonstrated estimated glomerular filtration rate (eGFR) preservation (+2.90\u2005mL\/min\/1.73\u2005m2\/year; 95% CI: 0.94 to 4.86) and urine albumin-to-creatinine ratio reduction (\u221225.0%; 95% CI: \u221236.0% to \u221213.0%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Tirzepatide produces consistent anti-inflammatory effects and significant natriuretic peptide reductions, supported by moderate Grading of Recommendations Assessment, Development and Evaluation certainty. Evidence for functional and renal outcomes remains limited to single-trial analyses and should be considered hypothesis-generating pending larger dedicated heart failure trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO Registration<\/jats:title>\n                    <jats:p>CRD42026137255<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgag284","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T11:45:43Z","timestamp":1791632743000},"source":"Crossref","is-referenced-by-count":0,"title":["Effects of tirzepatide (GIP\/GLP-1 dual receptor agonist) on cardiorenal biomarkers and functional capacity in heart failure: a systematic review and meta-analysis"],"prefix":"10.1210","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2963-7259","authenticated-orcid":false,"given":"Naseem","family":"Eisa","sequence":"first","affiliation":[{"name":"Community Health Partners , Community Medical Centers, Fresno, CA 93720 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5826-447X","authenticated-orcid":false,"given":"Mira","family":"Khoury","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Damascus University , Damascus PO Box 30621 ,","place":["Syria"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"issue":"9","key":"2026101310330456500_dgag284-B1","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/s41569-020-0363-2","article-title":"Evaluation and management of heart failure with preserved ejection fraction","volume":"17","author":"Borlaug","year":"2020","journal-title":"Nat Rev Cardiol"},{"issue":"36","key":"2026101310330456500_dgag284-B2","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur Heart J"},{"issue":"12","key":"2026101310330456500_dgag284-B3","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"},{"issue":"3","key":"2026101310330456500_dgag284-B4","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1056\/NEJMoa2206038","article-title":"Tirzepatide once weekly for the treatment of obesity","volume":"387","author":"Jastreboff","year":"2022","journal-title":"N Engl J Med"},{"issue":"5","key":"2026101310330456500_dgag284-B5","doi-asserted-by":"crossref","first-page":"427\u2013","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"},{"issue":"6","key":"2026101310330456500_dgag284-B6","doi-asserted-by":"crossref","first-page":"102099","DOI":"10.1016\/j.disamonth.2026.102099","article-title":"Efficacy and safety of tirzepatide in patients with heart failure with preserved ejection fraction: a systematic review and meta-analysis","volume":"72","author":"Sebastian","year":"2026","journal-title":"Dis Mon"},{"issue":"2","key":"2026101310330456500_dgag284-B7","doi-asserted-by":"crossref","first-page":"544\u2013","DOI":"10.1038\/s41591-024-03374-z","article-title":"Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial","volume":"31","author":"Borlaug","year":"2025","journal-title":"Nat Med"},{"issue":"19","key":"2026101310330456500_dgag284-B8","doi-asserted-by":"crossref","first-page":"1430\u2013","DOI":"10.1161\/CIRCULATIONAHA.124.072889","article-title":"The association between tirzepatide versus insulin glargine and NT-proBNP levels in people with type 2 diabetes","volume":"151","author":"Sattar","year":"2025","journal-title":"Circulation"},{"key":"2026101310330456500_dgag284-B9","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"2026101310330456500_dgag284-B10","unstructured":"Eisa N, Khoury M. Published online 2025. Supplemental data from Eisa et al., Effects of Tirzepatide (GIP\/GLP-1 Dual Receptor Agonist) on Cardiorenal Biomarkers and Functional Capacity in Heart Failure: A Systematic Review and Meta-Analysis. Deposited in Figshare. 10.6084\/m9.figshare.32975291"},{"key":"2026101310330456500_dgag284-B11","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"Rob 2: a revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"2026101310330456500_dgag284-B12","doi-asserted-by":"crossref","first-page":"i4919","DOI":"10.1136\/bmj.i4919","article-title":"ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions","volume":"355","author":"Sterne","year":"2016","journal-title":"BMJ"},{"issue":"7650","key":"2026101310330456500_dgag284-B13","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1136\/bmj.39489.470347.AD","article-title":"GRADE: an emerging consensus on rating quality of evidence and strength of recommendations","volume":"336","author":"Guyatt","year":"2008","journal-title":"BMJ"},{"issue":"1","key":"2026101310330456500_dgag284-B14","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1471-2288-14-25","article-title":"The Hartung-Knapp-Sidik-Jonkman method for random effects meta-analysis","volume":"14","author":"IntHout","year":"2014","journal-title":"BMC Med Res Methodol"},{"issue":"1","key":"2026101310330456500_dgag284-B15","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/dom.14553","article-title":"Tirzepatide improves cardiovascular risk biomarkers in patients with type 2 diabetes: a post hoc analysis","volume":"24","author":"Wilson","year":"2022","journal-title":"Diabetes Obes Metab"},{"issue":"6","key":"2026101310330456500_dgag284-B16","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1056\/NEJMoa2107519","article-title":"Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes","volume":"385","author":"Fr\u00edas","year":"2021","journal-title":"N Engl J Med"},{"issue":"10295","key":"2026101310330456500_dgag284-B17","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0140-6736(21)01324-6","article-title":"Efficacy and safety of tirzepatide in patients with type 2 diabetes (SURPASS-1)","volume":"398","author":"Rosenstock","year":"2021","journal-title":"Lancet"},{"issue":"4","key":"2026101310330456500_dgag284-B18","first-page":"e82118","article-title":"Evaluating the impact of tirzepatide on clinical outcomes in patients with heart failure","volume":"17","author":"Bin Abdul Malik","year":"2025","journal-title":"Cureus"},{"issue":"4","key":"2026101310330456500_dgag284-B19","doi-asserted-by":"crossref","first-page":"102998","DOI":"10.1016\/j.cpcardiol.2025.102998","article-title":"Real-world efficacy of tirzepatide in patients with heart failure without diabetes","volume":"50","author":"Augusto","year":"2025","journal-title":"Curr Probl Cardiol"},{"issue":"4","key":"2026101310330456500_dgag284-B20","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jacc.2013.02.092","article-title":"A novel paradigm for heart failure with preserved ejection fraction","volume":"62","author":"Paulus","year":"2013","journal-title":"J Am Coll Cardiol"},{"issue":"1","key":"2026101310330456500_dgag284-B21","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s11154-025-09991-4","article-title":"Anti-inflammatory effects of tirzepatide: a systematic review and meta-analysis","volume":"27","author":"Masson","year":"2026","journal-title":"Rev Endocr Metab Disord"},{"issue":"24","key":"2026101310330456500_dgag284-B22","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1056\/NEJMoa2307563","article-title":"Semaglutide and cardiovascular outcomes in obesitywithout diabetes","volume":"389","author":"Lincoff","year":"2023","journal-title":"N Engl J Med"},{"issue":"4","key":"2026101310330456500_dgag284-B23","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.3390\/ijms21041509","article-title":"GIP as a potential therapeutic target for atherosclerotic cardiovascular disease","volume":"21","author":"Mori","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"1","key":"2026101310330456500_dgag284-B24","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1001\/jama.2015.17346","article-title":"Effect of caloric restriction or aerobic exercise training in obese older patients with HFpEF","volume":"315","author":"Kitzman","year":"2016","journal-title":"JAMA"},{"issue":"15","key":"2026101310330456500_dgag284-B25","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"},{"issue":"20","key":"2026101310330456500_dgag284-B26","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1016\/j.jacc.2020.09.542","article-title":"Interpreting the Kansas City cardiomyopathy questionnaire","volume":"76","author":"Spertus","year":"2020","journal-title":"J Am Coll Cardiol"},{"issue":"16","key":"2026101310330456500_dgag284-B27","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1056\/NEJMoa2107038","article-title":"Empagliflozin in heart failure with a preserved ejection fraction","volume":"385","author":"Anker","year":"2021","journal-title":"N Engl J Med"},{"issue":"1","key":"2026101310330456500_dgag284-B28","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1161\/CIRCULATIONAHA.116.021884","article-title":"Phenotype-specific treatment of heart failure with preserved ejection fraction","volume":"134","author":"Shah","year":"2016","journal-title":"Circulation"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgag284\/71909725\/dgag284.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgag284\/71909725\/dgag284.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:33:11Z","timestamp":1791901991000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article\/doi\/10.1210\/clinem\/dgag284\/8914420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,13]]},"references-count":28,"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgag284","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,13]]},"article-number":"dgag284"}}