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Semaglutide for Symptom Management in HFpEF and Related Metabolic Phenotypes Kimmy Nguyen Jul 24, 2025 5 min read Updated: Sep 13, 2025 Written by Alex Flores-Xie, PharmD Candidate 2026 and Adenike Atanda-Oshikoya, PharmD, BCACP, CDCES, CTTS HFpEF: A Growing Challenge Heart Failure (HF) is a heterogenous syndrome defined by structural or functional cardiac abnormalities impairing the hearts ability to meet metabolic demands.(1,2) HF is classified by left-ventricular ejection fraction (LVEF) into: HF with reduced EF (HFrEF, LVEF 40%).(1) With over 80% of patients with HFpEF being overweight or obese, this phenotype accounts for most HF cases in the United States and continues to rise in prevalence.(3) Obesity worsens clinical outcomes via cardiac adverse remodeling.(4) Excess adiposity contributes to HFpEF progression through increased leptin levels, reduced natriuretic peptides, and activation of the renin-angiotensin-aldosterone system (RAAS), leading to systemic inflammation, cardiac fibrosis, and arterial stiffness.(3) Patients with HFpEF, obesity, and diabetes experience greater adverse hemodynamics, worse functional capacity, and quality of life.(4) HFpEF, accounts for up to 50% of HF hospitalizations.(2) Hospitalized patients are often older females with obesity, type 2 diabetes mellitus (T2DM), hypertension, atrial fibrillation, and chronic kidney disease