{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:28:47Z","timestamp":1790810927226,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 113\u20102314\u2010B\u2010A49\u2010040\u2010MY3"],"award-info":[{"award-number":["NSTC 113\u20102314\u2010B\u2010A49\u2010040\u2010MY3"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 113\u20102314\u2010B\u2010A4"],"award-info":[{"award-number":["NSTC 113\u20102314\u2010B\u2010A4"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Heart failure with preserved ejection fraction (HFpEF) presents a therapeutic challenge, characterised by a paucity of validated treatments. Emerging data suggest that targeting adiposity is central to HFpEF pathogenesis. We conducted an updated network meta\u2010analysis to compare the efficacy of emerging and established HFpEF therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We systematically searched PubMed, Embase and Cochrane Library from inception to April 2025 for randomised controlled trials enrolling patients with HFpEF and evaluating pharmacotherapies, including angiotensin\u2010converting enzyme inhibitors, angiotensin receptor blockers, beta blockers, mineralocorticoid receptor antagonists (MRAs), digoxin, angiotensin receptor\u2010neprilysin inhibitor, sodium\u2010glucose transporter 2 inhibitors (SGLT2is), glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101 RAs), nitrates and nitrites. The primary outcome was a composite of cardiovascular death and heart failure (HF) hospitalisation. The secondary outcomes included cardiovascular death, all\u2010cause mortality, worsening HF events, change in the 6\u2010min walk test (6MWT) distance, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ\u2010CSS) and N\u2010terminal pro\u2010B\u2010type natriuretic peptide levels. A frequentist random\u2010effects NMA was conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty\u2010nine trials with 78 treatment arms and 48\u2009235 patients were enrolled. Compared with placebo, GLP\u20101 RAs (HR: 0.73, 95% CI 0.61\u20130.88) and SGLT2is (HR: 0.79, 95% CI 0.70\u20130.90; P\u2010score: 0.807) significantly reduced the risk of cardiovascular death and HF hospitalisation. GLP\u20101 RAs showed the highest probability of ranking first (P\u2010score: 0.871). GLP\u20101 RAs elicited the greatest improvement in functional outcomes, including the 6MWT (mean difference: +17.60\u2009m, 95% CI 8.53\u201326.67) and KCCQ\u2010CSS (mean difference: +7.38 points, 95% CI 5.51\u20139.26). No statistically significant differences in cardiovascular death or all\u2010cause mortality were observed among the treatments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients with HFpEF, GLP\u20101RA, SGLT2i and MRA significantly reduced the risk of cardiovascular death and HF hospitalisation, while GLP\u20101RA additionally improved the functional and quality\u2010of\u2010life outcomes. GLP\u20101RA and SGLT2i significantly reduced HF morbidity, and GLP\u20101RA uniquely improved functional status, positioning adiposity modulation as a central therapeutic target in HFpEF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70503","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T06:09:21Z","timestamp":1769494161000},"page":"3137-3145","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Comparative effectiveness of pharmacotherapy for heart failure with preserved ejection fraction: A systematic review and network meta\u2010analysis"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4557-9097","authenticated-orcid":false,"given":"Szu\u2010Han","family":"Chen","sequence":"first","affiliation":[{"name":"School of Medicine, College of Medicine National Yang Ming Chiao Tung University  Taipei 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