Obesity, heart failure with preserved ejection fraction, and the role of glucagon-like peptide-1 receptor agonists - PubMed
Review
. 2024 Apr;11(2):649-661.
doi: 10.1002/ehf2.14560. Epub 2023 Dec 13.
Affiliations
- PMID: 38093506
- PMCID: PMC10966224
- DOI: 10.1002/ehf2.14560
Review
Obesity, heart failure with preserved ejection fraction, and the role of glucagon-like peptide-1 receptor agonists
Giuliana Cimino et al. ESC Heart Fail. 2024 Apr.
Abstract
Heart failure with preserved ejection fraction (HFpEF) has a high prevalence, affecting more than 50% of patients with heart failure. HFpEF is associated with multiple comorbidities, and obesity is one of the most common. A distinct phenotype has been proposed for obese patients with HFpEF. Recent data show the beneficial role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for weight loss in diabetic and non-diabetic patients with obesity or overweight when given as adjunctive therapy to diet and exercise. The mechanisms of action are related to paracrine and endocrine signalling pathways within the gastrointestinal tract, pancreas, and central nervous system that delay gastric emptying, decrease appetite, augment pancreatic beta-cell insulin secretion, and suppress pancreatic glucagon release. These drugs are therefore potentially indicated for treatment of patients with HFpEF and obesity or overweight. Efficacy and safety need to be shown by clinical trials with a first one, Semaglutide Treatment Effect in People with obesity and heart failure with preserved ejection fraction (STEP HFpEF), recently concluded. The aim of the present review is to provide the pathophysiological and pharmacological rationale for GLP-1 RA administration to obese patients with HFpEF.
Keywords: Glucagon‐like peptide‐1 receptor agonists; Heart failure with preserved ejection fraction; Obesity.
© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
Figures

Direct and indirect effects of glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) in heart failure with preserved ejection fraction (HFpEF). The figure shows currently known or suggested direct and indirect effects of GLP‐1 RA in HFpEF in all human organs.

Reduction of adverse events in type 2 diabetes patients treated with glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs). The figure is adapted from Sattar et al., showing the beneficial effects on mortality, hospital admission for heart failure (HF), and MACE meta‐analysed from GLP‐1 RA clinical trials (ELIXA, LEADER, SUSTAIN‐6, EXSCEL, Harmony Outcomes, REWIND, PIONEER 6, and AMPLITUDE‐O). MACE included cardiovascular death, myocardial infarction, and stroke. X axis represents the % reduction of the analysed endpoints. CI, confidence interval; HR, hazard ratio; MACE, major adverse cardiovascular events.

Obesity and heart failure with preserved ejection fraction (HFpEF). The figure shows the clinical feature and pathophysiology of obesity and HFpEF and the potential benefit deriving from glucagon‐like peptide‐1 receptor agonists. LV, left ventricular.
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