{"doi":"10.1016/j.jchf.2025.102660","title":"Semaglutide and Exercise Function in Obesity-Related HFpEF","abstract":"BACKGROUND: Exercise function quantified by 6-minute walk distance (6MWD) is severely impaired in patients with heart failure with preserved ejection fraction (HFpEF). OBJECTIVES: This prespecified secondary analysis of pooled data from the STEP-HFpEF Program (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity) examined factors associated with impaired exercise function at baseline, detailed effects of semaglutide on 6MWD, and on other key trial endpoints according to baseline 6MWD in patients with HFpEF. METHODS: Associates of 6MWD were assessed at baseline, and effects of semaglutide on 6MWD were evaluated at early (20 weeks) and final (52 weeks) time points, across subgroups, and according to the magnitude of weight loss achieved. Effects of semaglutide on the dual primary (changes in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score [KCCQ-CSS] and body weight) and secondary/exploratory endpoints were contrasted by tertiles of baseline 6MWD. RESULTS: = NS). Each 1-unit decrease in body mass index on treatment with semaglutide was associated with a 4.1 m (95% CI: 2.4-5.7 m) increase in 6MWD (P < 0.0001). CONCLUSIONS: In patients with obesity-related HFpEF, impaired 6MWD is most strongly associated with excess adiposity, congestion, and inflammation. Semaglutide-mediated improvements in HF-related symptoms, physical limitations, and exercise function were consistent across the spectrum of baseline 6MWD, observed as early as 20 weeks after the initiation of treatment, preceding maximal weight loss. The effects were consistent across subgroups. There was strong correlation between greater magnitude of weight loss and greater improvements in 6MWD. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF], NCT04788511; Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes [STEP-HFpEF DM], NCT04916470).","journal":"JACC Heart Failure","year":2025,"id":522165,"datarank":0.3276814307318036,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.05891751034759535,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.05891751034759535,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":5,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT04916470"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":260522,"name":"Dalane W. Kitzman","orcid":"0009-0000-5274-0826","position":1,"is_corresponding":false},{"id":1207818,"name":"Shachi Patel","orcid":null,"position":2,"is_corresponding":false},{"id":660606,"name":"Khaja Chinnakondepalli","orcid":"0000-0002-7405-8614","position":3,"is_corresponding":false},{"id":49613,"name":"Javed Butler","orcid":"0000-0001-7683-4720","position":4,"is_corresponding":false},{"id":257817,"name":"Melanie J. Davies","orcid":"0000-0002-9987-9371","position":5,"is_corresponding":false},{"id":57272,"name":"Mark C. Petrie","orcid":"0000-0002-6333-9496","position":6,"is_corresponding":false},{"id":235994,"name":"Sanjiv J. Shah","orcid":"0000-0002-5655-8201","position":7,"is_corresponding":false},{"id":57276,"name":"Subodh Verma","orcid":"0000-0002-4018-8533","position":8,"is_corresponding":false},{"id":885561,"name":"Julio Núñez","orcid":"0000-0003-1672-7119","position":9,"is_corresponding":false},{"id":1016192,"name":"Mette Nygaard Einfeldt","orcid":"0000-0003-2427-2601","position":10,"is_corresponding":false},{"id":1207820,"name":"Karoline Liisberg","orcid":null,"position":11,"is_corresponding":false},{"id":636401,"name":"Afshin Salsali","orcid":"0000-0003-2763-0486","position":12,"is_corresponding":false},{"id":57284,"name":"Mikhail Kosiborod","orcid":"0000-0002-3750-9789","position":13,"is_corresponding":false},{"id":230314,"name":"Barry A. Borlaug","orcid":"0000-0001-9375-0596","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T02:49:49.198144Z","pmid":"41045908","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}