The 2022 American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Failure Society of America (HFSA) Heart Failure Guidelines [1] and the 2023 European Society of Cardiology (ESC) guidelines [10] establish sodium-glucose cotransporter 2 (SGLT-2) inhibitors as foundational therapy for HFpEF, while emphasizing comprehensive management of key comorbidities (e.g., hypertension, diabetes, obesity). This evidence concerns the gene SLC5A2 and obesity due to melanocortin 4 receptor deficiency.