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GLP-1 for Treatment of Heart Failure
Panelists discuss how GLP-1 receptor agonists show promising benefits for patients with HFpEF, particularly those with obesity-related disease, through significant weight loss and improved functional capacity, while their role in HFrEF remains more cautious due to concerns about increased heart rate and potential arrhythmic risks, though observational data suggest additive benefits when combined with SGLT2 inhibitors.
EP: 1.Economic Burden of Heart Failure Care
EP: 2.Heart Failure Prevalence and Screening
EP: 3.Quality Metrics in Heart Failure
EP: 4.Heart Failure Stages and Impact of Delayed Diagnosis
EP: 5.Collaboration in Heart Failure Treatment
EP: 6.Guideline-Directed Medical Therapies in Heart Failure
EP: 7.β-Blockers for Treatment of Heart Failure
EP: 8.Role of Diuretics in Heart Failure Management
EP: 9.Treatment of Heart Failure With ARNI Therapy
EP: 10.SGLT2 Inhibitors for Treatment of Heart Failure
EP: 11.GLP-1 for Treatment of Heart Failure
EP: 12.Role of MRAs in Heart Failure Treatment
Glucagon-like peptide-1 (GLP-1) receptor agonists show particular promise in heart failure with preserved ejection fraction (HFpEF), especially among patients with obesity-related disease. The STEP-HFpEF trials demonstrate that substantial weight reduction achieved with once-weekly semaglutide or tirzepatide correlates with improvements in heart failure–related outcomes, functional capacity, and exercise tolerance. Meta-analyses of available data suggest potential signals for reduced cardiovascular events including heart failure hospitalizations, though definitive evidence requires larger dedicated trials.
The mechanistic rationale for GLP-1 therapy in HFpEF centers on addressing central adiposity, which may drive disease progression through “angry adipocyte” pathophysiology. By targeting obesity as a fundamental driver of HFpEF, these agents potentially address root causes rather than just symptoms. Additional benefits include improvements in comorbid conditions like sleep apnea and other obesity-related complications that contribute to heart failure progression.
Application in heart failure with reduced ejection fraction (HFrEF) requires more caution due to limited dedicated trial data and some concerning signals. The FIGHT trial showed potential signals for increased heart failure hospitalizations with liraglutide in hospitalized patients with HFrEF, though post hoc analyses of cardiovascular outcome trials suggest benefits may still exist in ambulatory, stable patients. Potential concerns include heart rate increases and arrhythmic risks, necessitating careful patient selection. However, for patients with compelling indications like obesity or diabetes, the SELECT trial subgroup data suggest HFrEF should not preclude GLP-1 therapy initiation when otherwise appropriate.
