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Key Clinical Trials of Therapies Demonstrating Benefit in HFpEF (7,8,12-14) A New Era in HFpEF Management Semaglutide offers significant benefits for patients with HFpEF, obesity, and T2DM, especially those at high CV risk.(12,13) Exploratory analyses suggest improvements in congestion, vascular and skeletal muscle function, mitochondrial efficiency, epicardial adipose tissue reduction, inflammation, and insulin resistance.(4) Loop diuretics remain essential for acute decompensation and symptom management but increase the risk of electrolyte and volume disturbances and renal dysfunction with chronic use.(2) While both diuretics and semaglutide alleviate congestion in HFpEF, semaglutide uniquely demonstrates clinically meaningful improvements in quality of life.(12,13) However, when compared to loop diuretics like furosemide, the high cost of semaglutide remains a barrier.(15) Current evidence, particularly from the echocardiographic substudies of the STEP-HFpEF trial program, suggests that semaglutides effects on congestion may extend beyond weight loss alone