Tirzepatide in the management of heart failure with preserved ejection fraction: A narrative review

Heart failure with preserved ejection fraction (HFpEF) is a growing clinical challenge, particularly in patients with obesity, where metabolic dysfunction, systemic inflammation, and endothelial impairment drive disease progression. Traditional therapies have shown limited benefit in this subgroup, highlighting the need for novel, phenotype-specific treatments. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, has demonstrated significant weight loss, improved insulin sensitivity, and potential cardiovascular benefits in recent clinical trials. This narrative review explores the pathophysiological overlap between obesity and HFpEF, summarizes key findings from the SURMOUNT and SURPASS trial programs, and examines emerging evidence from ongoing studies such as SUMMIT-HFpEF. The review also discusses tirzepatide’s potential mechanisms of action in improving diastolic function and vascular health, its safety profile, and its role in future multidrug strategies. Tirzepatide may represent a promising new direction in the metabolic management of HFpEF with obesity.