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Life sciences · Journal article
Clinical Nutrition Espen · November 5, 2026
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BACKGROUND & AIMS: Obesity is common in heart failure with reduced ejection fraction (HFrEF), but the functional, mechanistic, and safety consequences of intentional weight loss remain uncertain. Incretin-based therapies improve symptoms and functional capacity in obesity-related heart failure with preserved ejection fraction, whereas evidence in HFrEF is limited, and prior glucagon-like peptide-1 receptor agonist trials have raised safety concerns. The FIT-HF trial tests whether semaglutide-based weight loss is superior to intensive diet-based weight loss for improving exercise capacity in adults with obesity and stable HFrEF. METHODS: peak) from baseline to week 52, assessed by cardiopulmonary exercise testing. Supportive secondary endpoints include Kansas City Cardiomyopathy Questionnaire score, 6-min walk distance, left ventricular end-systolic volume assessed by cardiovascular magnetic resonance, high-sensitivity C-reactive protein, and N-terminal pro-B-type natriuretic peptide. Exploratory work packages assess safety, cardiac/pulmonary physiology, body composition, physical activity, and metabolic/biomarker responses. DISCUSSION: peak with multimodal phenotyping to interpret physiological profiles alongside achieved weight loss and body composition. CLINICAL TRIAL REGISTRATION: European Clinical Trials Information System: European Union trial number: CT-2023-503753-35-01; ClinicalTrials.gov identifier: NCT06423599.