Key result
SGLT2i, GLP-1 RAs, and non-steroidal MRAs demonstrate disease-modifying prognostic benefits in obesity-related HFpEF.
Why the study?
HFpEF constitutes over 50% of the global heart failure burden with obesity as a central driver, while recent advances in anti-obesity medications have redefined management strategies.
Novel pharmacological therapies targeting obesity and metabolic pathways offer significant clinical benefits and disease-modifying effects in patients with obesity-related HFpEF.
May guide drug selection in obesity-related HFpEF; leaves open need for confirmatory RCTs.
Heart failure with preserved ejection fraction (HFpEF) now constitutes over 50% of global heart failure (HF) burden, with obesity recognized as a central pathogenic driver. Recent advances in anti-obesity medication (AOM) have redefined management strategies. This review summarizes landmark developments: sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emerged as the first agents with robust prognostic benefit; Glucagon like peptide-1 receptor agonists (GLP-1RA) and Glucose dependent insulin peptide (GIP) and GLP-1 dual receptor agonists (e.g., Tirzepatide) demonstrate disease-modifying effects through weight loss and direct cardiac remodeling reversal; and the non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone shows enhanced efficacy in obese subgroups. We also critically analyze the “obesity paradox”, propose biomarker-guided phenotyping, and address translational challenges including cost accessibility and long-term efficacy sustainability. The latest adipokine hypothesis also elucidates the pathogenesis of HFpEF, and based on this hypothesis, some new pharmacological treatment strategies have been proposed. This article will also discuss this and differentiate the deposition of visceral fat and epicardial fat.
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Zhang et al. (2026) conducted a review in Obesity-related heart failure with preserved ejection fraction (HFpEF). Pharmacological therapies (SGLT2 inhibitors, GLP-1 receptor agonists, Tirzepatide, Finerenone) was evaluated. Recent pharmacological advances, including SGLT2 inhibitors, GLP-1 receptor agonists, and non-steroidal MRAs, demonstrate significant prognostic benefits and disease-modifying effects in patients with obesity-related HFpEF.
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