The Treatment of Obesity in the Context of the Obesity Paradox in Patients with Heart Failure: A Narrative Review

While excess adiposity is a known risk factor for incident heart failure ( HF), once the condition is established, observational data suggest that increased body mass index (BMI) may confer a survival advantage. This paradox has emphasized the underlying roles of cardiorespiratory fitness (CRF), and body composition, particularly lean mass (LM), in influencing clinical outcomes.

In this review, we explore the multifaceted nature of the obesity paradox in HF, with a focus on emerging anti-obesity incretin-mimetic therapies, such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. These agents have demonstrated remarkable efficacy in weight reduction and favorable cardiovascular profiles in patients with HF with preserved ejection fraction (EF), yet their use in other HF populations, such as HF with reduced EF, raises important clinical questions and the urgent need for future research. Concerns include the potential for LM loss, implications for sarcopenic obesity, and the uncertain impact of weight loss on outcomes in patients who may not benefit from weight loss. We also highlight the need to assess therapeutic outcomes beyond BMI, incorporating measures of CRF, such as peak oxygen consumption (VO₂ peak), quality of life, and functional capacity, using tools such as the 6-minute walk test. Barriers to implementation, including cost, provider hesitation, insurance restrictions, and patient level challenges are also reviewed.

Finally, we call for future research using contemporary cohorts and advanced phenotyping to reevaluate the obesity paradox in the context of modern pharmacologic interventions. As obesity treatment continues to evolve, a patient-centered, individualized approach that integrates body composition, functional status, and comorbid conditions will be essential in optimizing care for individuals with HF.