Introduction
Heart failure with preserved ejection fraction (HFpEF) is the most prevalent form of heart failure, frequently complicating cardiometabolic conditions such as obesity and type 2 diabetes. These comorbidities exacerbate symptom burden, functional impairment, and cardiovascular risk. Despite this substantial disease burden, effective treatments for HFpEF, particularly in populations with metabolic dysfunction, remain limited.
Recent randomized controlled trials have demonstrated that semaglutide—a glucagon-like peptide-1 (GLP-1) receptor agonist—and tirzepatide—a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist—improve clinical symptoms in obesity-related HFpEF. However, these studies were limited by small sample sizes, few clinical events, and restrictive eligibility criteria, limiting generalizability and impeding regulatory approval and clinical guideline incorporation.
