Volume 30, Issue 174, August 2026

Incretin-based pharmacotherapy in the obesity phenotype of heart failure with preserved ejection fraction - Pathophysiology and clinical evidence

Tomaszek Barbara^1♦, Łoś Aleksandra², Blok Aleksandra¹, Jakubczyk Inga², Szkodziński Kacper³, Wiater Dominik³, Płodzień Gabriela², Pempuś Wiktoria², Maternia Jagoda², Majowicz-Czaszyńska Karolina², Król Nikola²

¹The Independent Public Healthcare Institution in Przeworsk, Szpitalna 16, 37-200 Przeworsk, Poland
²Provincial Clinical Hospital No. 2 named after St. Jadwiga the Queen in Rzeszów, Lwowska 60, 35-301 Rzeszów, Poland
³Clinical Hospital named after Fryderyk Chopin, Szopena 2, 35-055 Rzeszów, Poland

^♦Corresponding author
Barbara Tomaszek, The Independent Public Healthcare Institution in Przeworsk, Szpitalna 16, 37-200 Przeworsk, Poland

ABSTRACT

Introduction: The most common form of heart failure encountered in clinical practice is heart failure with preserved ejection fraction (HFpEF). It usually affects patients who are overweight. There is an association between increased epicardial and visceral fat and chronic inflammation, microvascular dysfunction, and impaired relaxation of the heart chambers. This review aimed to explore GLP-1 receptor agonists (GLP-1 RA) and dual incretin agonists (GIP/GLP-1 RA) - tirzepatide, in patients with HFpEF and obesity. Methods: In this review, we have examined current literature on GLP 1 RA (like semaglutide and GIP/GLP 1 receptor agonists in patients with HFpEF associated with obesity. We concentrated primarily on large-scale randomized trials (STEP HFpEF, STEP-HFpEF DM, SUMMIT). To illustrate the effects of these therapies on clinical outcomes, biomarkers, and epicardial fat, additional imaging and mechanistic work were taken into account. Results and Discussion: The findings show that incretin drugs help patients with HFpEF and obesity lose a meaningful amount of weight. Moreover, they lower NT proBNP levels, reduce inflammation, and improve patient functioning. With tirzepatide, the SUMMIT trial reported fewer cardiovascular deaths or worsening heart failure episodes and a decline in epicardial fat volume on cardiac MRI. We conclude that adding incretin therapy to standard treatment is a promising way to ease symptoms in patients with HFpEF and obesity.

Keywords: HFpEF, GLP-1 agonist, tirzepatide, semaglutide, epicardial adipose tissue

Medical Science, 2026, 30, e151ms3920

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Published: 16 August 2026