Trial reportJACC. Heart failure2025
Semaglutide and Exercise Function in Obesity-Related HFpEF: Insights From the STEP-HFpEF Program.
Trial report in JACC. Heart failure, 2025. The graph read 2 numbers from its abstract, feeding 1 cell of the map, but it casts no vote: it is a later paper about NCT04788511, whose primary report (PMID 37622681) speaks for the trial. It reports registered trial NCT04788511. Cited by 5 papers.
What it found
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Treatment with semaglutide increased 6MWD compared with placebo, an effect apparent at 20 weeks (treatment difference 14.6 m [95% CI: 8.6-20.7 m]; P < 0.0001) that was maintained at 52 weeks (treatment difference 17.1 m [95% CI: 9.2-25.0 m]; P < 0.0001).
Treatment with semaglutide increased 6MWD compared with placebo, an effect apparent at 20 weeks (treatment difference 14.6 m [95% CI: 8.6-20.7 m]; P < 0.0001) that was maintained at 52 weeks (treatment difference 17.1 m [95% CI: 9.2-25.0 m]; P < 0.0001).
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Where it lands on the map
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What it adds to each cell
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GLP-1 receptor agonists×cardiac & vascular function
Does not voteOpen on the map →What to test next →6 readable studies in this cell: 3 favour the treatment, 2 find no difference, 1 favour the comparator.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effect of Semaglutide 2.4 mg Once Weekly on Function and Symptoms in Subjects With Obesity-related Heart Failure With Preserved Ejection Fraction
Open the trial in the graphEffect of Semaglutide 2.4 mg Once-weekly on Function and Symptoms in Subjects With Obesity-related Heart Failure With Preserved Ejection Fraction, and Type 2 Diabetes
Who cites it
5 citing papers in PubMed.
- Heart Failure with Reduced versus Preserved Ejection Fraction: Molecular Mechanisms, Immunologic Pathways, Current Therapies, and Future Directions.Archives of internal medicine research · 2026Article
- Diabetes, Adiposity, and Functional Phenotypes in HFpEF: A Systematic Review of Recent Treatment-Response Evidence.Cureus · 2026Review
- Glucagon-like Peptide-1 Therapy in Obesity-Related Heart Failure with Preserved Ejection Fraction: Mechanisms, Clinical Evidence, and Implications.Journal of clinical medicine · 2026Review
- Obesity and Heart Failure: Introducing the Theme.Journal of cardiovascular development and disease · 2026Review
- Mitochondrial-inflammatory coupling in HFpEF: an emerging mechanistic framework for understanding the cardioprotective effects of SGLT2 inhibitors.Frontiers in cardiovascular medicine · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
Abstract
The marked sentences are the ones the graph read a number from.
backgroundExercise function quantified by 6-minute walk distance (6MWD) is severely impaired in patients with heart failure with preserved ejection fraction (HFpEF).
objectivesThis 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.
methodsAssociates 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.
resultsThe authors randomized 1,145 patients to semaglutide or placebo. Compared with patients who had obesity-related HFpEF and higher 6MWD, those with lower 6MWD were older and had lower KCCQ-CSS, higher body mass index and waist circumference, greater systemic inflammation (higher C-reactive protein), and more severe congestion (higher N-terminal pro-B-type natriuretic peptide, more diuretic use). Treatment with semaglutide increased 6MWD compared with placebo, an effect apparent at 20 weeks (treatment difference 14.6 m [95% CI: 8.6-20.7 m]; P < 0.0001) that was maintained at 52 weeks (treatment difference 17.1 m [95% CI: 9.2-25.0 m]; P < 0.0001). Increases in 6MWD with semaglutide (vs placebo) were similar across all relevant subgroups, with no significant interactions. Treatment with semaglutide increased KCCQ-CSS and reduced body weight, reduced C-reactive protein, improved the hierarchical composite (death, heart failure events, change in KCCQ-CSS and 6MWD), and reduced N-terminal pro-B-type natriuretic peptide across the spectrum of baseline 6MWD (all P
conclusionsIn 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).
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.