eprintid: 310913 rev_number: 11 eprint_status: archive userid: 37347 dir: disk0/00/31/09/13 datestamp: 2024-04-23 15:43:50 lastmod: 2024-04-24 09:17:11 status_changed: 2024-04-23 15:43:50 type: article metadata_visibility: show sword_depositor: 37347 creators_name: Borlaug, Barry A. creators_name: Kitzman, Dalane W. creators_name: Davies, Melanie J. creators_name: Rasmussen, Søren creators_name: Barros, Eric creators_name: Butler, Javed creators_name: Einfeldt, Mette Nygaard creators_name: Hovingh, G. Kees creators_name: Møller, Daniél Vega creators_name: Petrie, Mark C. creators_name: Shah, Sanjiv J. creators_name: Verma, Subodh creators_name: Abhayaratna, Walter creators_name: Ahmed, Fozia Z. creators_name: Chopra, Vijay creators_name: Ezekowitz, Justin creators_name: Fu, Michael creators_name: Ito, Hiroshi creators_name: Lelonek, Małgorzata creators_name: Melenovsky, Vojtech creators_name: Núñez, Julio creators_name: Perna, Eduardo creators_name: Schou, Morten creators_name: Senni, Michele creators_name: van der Meer, Peter creators_name: Von Lewinski, Dirk creators_name: Wolf, Dennis creators_name: Kosiborod, Mikhail N. creators_orcid: 0000-0002-6333-9496 title: Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial ispublished: pub divisions: 25200000 note: This trial was sponsored by Novo Nordisk and is registered with ClinicalTrials.gov (NCT04788511). [...] B.A.B. is supported, in part, by National Institutes of Health (NIH) grants R01 HL128526, R01 HL162828 and U01 HL160226 and by US Department of Defense grant W81XWH2210245. M.J.D. is supported by Leicester National Institute for Health Research (NIHR) Biomedical Research Centre, Leicester General Hospital. D.W.K. is supported, in part, by NIH grants U01AG076928, R01AG078153, R01AG045551, R01AG18915, P30AG021332, U24AG059624 and U01HL160272. S.V. is supported by the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Canada and holds the Canada Research Chair in Cardiovascular Surgery. M.C.P. is supported by the British Heart Foundation Centre of Research Excellence Award (RE/13/5/30177 and RE/18/6/34217+). S.J.S. was supported by research grants from the NIH (U54 HL160273, R01 HL107577, R01 HL127028, R01 HL140731 and R01 HL149423). D.W. is a member of SFB1425, funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation). abstract: In the STEP-HFpEF trial, semaglutide improved symptoms, physical limitations and exercise function and reduced body weight in patients with obesity phenotype of heart failure and preserved ejection fraction (HFpEF). This prespecified analysis examined the effects of semaglutide on dual primary endpoints (change in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) and body weight) and confirmatory secondary endpoints (change in 6-minute walk distance (6MWD), hierarchical composite (death, HF events, change in KCCQ-CSS and 6MWD) and change in C-reactive protein (CRP)) across obesity classes I–III (body mass index (BMI) 30.0–34.9 kg m−2, 35.0–39.9 kg m−2 and ≥40 kg m−2) and according to body weight reduction with semaglutide after 52 weeks. Semaglutide consistently improved all outcomes across obesity categories (P value for treatment effects × BMI interactions = not significant for all). In semaglutide-treated patients, improvements in KCCQ-CSS, 6MWD and CRP were greater with larger body weight reduction (for example, 6.4-point (95% confidence interval (CI): 4.1, 8.8) and 14.4-m (95% CI: 5.5, 23.3) improvements in KCCQ-CSS and 6MWD for each 10% body weight reduction). In participants with obesity phenotype of HFpEF, semaglutide improved symptoms, physical limitations and exercise function and reduced inflammation and body weight across obesity categories. In semaglutide-treated patients, the magnitude of benefit was directly related to the extent of weight loss. Collectively, these data support semaglutide-mediated weight loss as a key treatment strategy in patients with obesity phenotype of HFpEF. ClinicalTrials.gov identifier: NCT04788511. date: 2023-08-27 date_type: published publisher: Nature Research id_number: 10.1038/s41591-023-02526-x copyright_holders: Copyright: © The Author(s) 2023 prior: First published in Nature Medicine 29(9): 2358–2365 repro: Reproduced under a Creative Commons licence uniqueid: glaseprints:2023-310913 issn_online: 1546-170X funding_project_code: 190814 funding_project_code: 303944 funding_project_name: BHF centre of excellence funding_project_name: BHF Centre of Excellence funding_investigator_name: Rhian Touyz funding_investigator_name: Colin Berry funding_funder_name: British Heart Foundation (BHF) funding_funder_name: British Heart Foundation (BHF) funding_funder_code: RE/13/5/30177 funding_funder_code: RE/18/6/34217 funding_investigator_dept: School of Cardiovascular & Metabolic Health funding_investigator_dept: SCMH - Cardiovascular & Metabolic Health pubmed_id: 37635157 euro_pubmed_id: 37635157 pmcid: PMC10504076 full_text_status: public publication: Nature Medicine volume: 29 number: 9 pagerange: 2358-2365 refereed: TRUE issn: 1078-8956 oa_research_materials_ack: No hoa_compliant: 9205 hoa_ref_pan: AB hoa_date_acc: 2023-08-01 hoa_date_pub: 2023-08-27 hoa_date_fcd: 2024-04-23 hoa_date_foa: 2024-04-23 hoa_version_fcd: VoR hoa_ex_dep: f hoa_exclude: FALSE hoa_gold: TRUE citation: Borlaug, B. A. et al. (2023) Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial. Nature Medicine , 29(9), pp. 2358-2365. (doi: 10.1038/s41591-023-02526-x ) (PMID:37635157) (PMCID:PMC10504076) document_url: https://eprints.gla.ac.uk/310913/2/310913.pdf