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Review
. 2025 Jan;30(1):131-136.
doi: 10.1007/s10741-024-10450-6. Epub 2024 Oct 19.

GLP-1 receptor agonists as promising anti-inflammatory agents in heart failure with preserved ejection fraction

Giovanni Battista Bonfioli  1 , Luca Rodella  1 , Marco Metra  1 , Enrico Vizzardi  2
Affiliations
Review

GLP-1 receptor agonists as promising anti-inflammatory agents in heart failure with preserved ejection fraction

Giovanni Battista Bonfioli et al. Heart Fail Rev. 2025 Jan.

Abstract

Heart Failure with Preserved Ejection Fraction (HFpEF) represents a significant challenge in modern cardiovascular medicine, characterized by diastolic dysfunction and a chronic pro-inflammatory milieu. The high prevalence of comorbidities such as diabetes, visceral obesity, and aging, which contribute to systemic inflammation, plays a pivotal role in the pathogenesis and progression of HFpEF. Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs), a class of glucose-lowering drugs, have demonstrated a wide range of pleiotropic effects that extend beyond glycaemic control. These effects include the reduction of inflammation and oxidative stress, vasodilation, decreased arterial stiffness, and a reduction in myocardial fibrosis-key factors in the pathophysiology of HFpEF. Recent evidence from the STEP-HFpEF and STEP-HFpEF-DM trials provides the first robust data supporting the efficacy of GLP-1 RAs, specifically semaglutide, in improving the quality of life in obese patients with HFpEF. These trials also demonstrated a significant reduction in C-Reactive Protein (CRP) levels, reinforcing the hypothesis that suppressing the pro-inflammatory state may yield substantial clinical benefits in this patient population. These findings suggest that GLP-1 RAs could play a crucial role in the management of HFpEF, particularly in patients with obesity, by targeting the underlying inflammatory processes and contributing to better overall cardiovascular outcomes.

Keywords: GLP-1; Heart Failure with Preserved Ejection Fraction; Inflammation.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Visual representation of GLP1-RA pleotropic effects. GLP1-RA not only act on glycemic levels through the action on pancreatic β-cells, but also have many other effects that include weight loss both for a local action of slowed gastric emptying, but also for a central action of a reduction of hunger, and also cardiovascular, renal and hepatic protection
Fig. 2
Fig. 2
GLP-1 RAs may lead to a reduction of systemic inflammation through different mechanisms that include: (i) their direct effects on glycaemic levels; (ii) the reduction of body weight, epicardial adipose tissue and consequently of pro-inflammatory adipokines; (iii) the reduction of inflammatory response through different mechanisms as the reduction of the activity of NF-kB pattern and the reduction of different inflammatory biomarkers such as CRP. The reduction of systemic inflammatory response is associated with atherosclerotic plaque stabilization and improvement of diastolic function in HFpEF
See this image and copyright information in PMC

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