Targeting obesity for therapeutic intervention in heart failure patients

Heart failure with preserved ejection fraction (HFpEF) is a highly heterogeneous syndrome, making it challenging to improve prognosis with pharmacotherapy. Obesity is one of the leading phenotypes of HFpEF, and its prevalence continues to grow worldwide. Consequently, obesity-targeted interventions have attracted attention as a novel treatment strategy for HFpEF.

The authors review the association between the pathogenesis of obesity and HFpEF and the potential for obesity-targeted pharmacotherapeutic strategies in HFpEF, together with the latest evidence. The literature search was conducted in PubMed up to April 2024.

The STEP HFpEF (Semaglutide Treatment Effect in People with obesity and HFpEF) and SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) trials recently demonstrated that the glucagon-like peptide 1 analogue, semaglutide, improves various aspects of clinical outcomes in obese HFpEF patients and significantly reduces cardiovascular and heart failure events in non-diabetic obese patients, along with a substantial weight loss. Future clinical trials with other incretin mimetics with more potent weight loss and sub-analyses of the SELECT trial may further emphasize the importance of the obesity phenotype-based approach in the treatment of HFpEF.