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Cited by 16Heart Failure Treatment and ManagementCardiovascular Disease and AdiposityCardiovascular Function and Risk Factors

Refining the link between obesity and heart failure: insights from GLP-1 receptor agonist trials and studies adopting direct adiposity measures

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Pugliese, Nicola Riccardo, Paneni, Francesco, Tricò, Domenico, Bacca, Alessandra Violet, De Biase, Nicolò, Dalpiaz, Hermann, Mengozzi, Alessandro, Virdis, Agostino +5 more·2025·Cardiovascular Diabetology
DOI 10.1186/s12933-025-02778-6PMC PMC12096527
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Abstract

Overweight and obesity are major risk factors for heart failure (HF), contributing to its development through metabolic, neurohormonal, haemodynamic, and inflammatory alterations. While overweight/obesity increases the risk of developing HF, its impact on patient outcomes remains complex. The "obesity paradox" suggests that a higher BMI may be associated with improved survival in patients with established HF. However, recent GLP-1 receptor agonist (GLP-1 RA) trials suggest that intentional weight loss positively influences outcomes in overweight/obese patients with HF. This seemingly contradictory evidence highlights the need for a deeper understanding of the mechanisms linking adiposity to HF outcomes. A more precise characterization of adiposity phenotypes using alternative and accurate measures of pathological fat accumulation is crucial in identifying individuals who may benefit most from anti-obesity treatments. In this context, recent research underscores the role of epicardial adipose tissue (EAT) in HF pathophysiology, as it directly influences cardiac function and structure through inflammatory, metabolic, and mechanical effects. This narrative review summarises current evidence on the impact of weight loss on HF outcomes, focusing on recent GLP-1 RA trial results. Additionally, it highlights epidemiological and molecular data supporting EAT as a novel adiposity measure that might allow refining patient selection for pharmacological weight-loss treatments. Finally, it emphasizes the need for future research to identify causal pathways linking alternative measures of visceral fat accumulation to HF outcomes. These efforts will be essential in optimizing the benefits of novel weight-loss treatments, ensuring effective and individualized therapeutic strategies for overweight or obese patients with HF.

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  • In trials with GLP-1RAs, the relationship between baseline adiposity phenotypes and their changes with treatment, with subsequent ischaemic MACE, remains undefined.

    “In trials with GLP-1RAs, the relationship between baseline adiposity phenotypes and their changes with treatment, with subsequent ischaemic major adverse cardiovascular events (MACE), remains undefined.10”

    From Semaglutide and cardiovascular outcomes by baseline and changes in adiposity measurements: a prespecified analysis of the SELECT trial (2025) · cites this paper as [10]

    The Conclusions (page unavailable) say that mechanisms linking GLP-1RA treatment to heart-failure prognosis remain unclear, and the adiposity section discusses treatment-related changes in epicardial fat. Neither passage addresses whether baseline adiposity phenotypes or their changes predict subsequent ischaemic MACE in GLP-1RA trials; searches for that relationship found no such passage in our copy. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Pugliese, N. R., Paneni, F., Tricò, D., Bacca, A. V., De Biase, N., Dalpiaz, H., Mengozzi, A., Virdis, A., Ghiadoni, L., Taddei, S., Kreutz, R., Tsioufis, K., & Masi, S.
Affiliations
  • University of Pisa (IT)
  • University of Zurich (CH)
  • Azienda Ospedaliera Universitaria Pisana (IT)
  • Charité – Universitätsmedizin Berlin (DE)
  • National and Kapodistrian University of Athens (GR)
Corresponding author
Masi, Stefano
ORCID
Venue
Cardiovascular Diabetology
Publisher
Springer Science and Business Media LLC
Published
2025-05-22
Volume
24
Issue
1
Pages
224-224
ISSN
1475-2840 (ISSN-L)
DOI
10.1186/s12933-025-02778-6
PMC
PMC12096527
OpenAlex
W4410575468
Cited by
16
References
27
Citations by year
2026: 10 · 2025: 6
FWCI
2.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Cardiovascular Diabetology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by-nc-nd)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • Swiss National Science Foundation to Francesco Paneni (310030_197557)
  • Swiss Heart Foundation to Francesco Paneni (FF19045)
  • European Union–NextGenerationEU through the Italian Ministry of University and Research under PNRR-M4C2-I1.3 (PE_00000019 “HEAL ITALIA” to Stefano Taddei, CUP I53C22001440006)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Keywords
obesity, heart failure, obesity paradox, GLP-1 receptor agonists, weight loss, epicardial adipose tissue, adiposity measures, visceral fat, overweight, patient selection, cardiac function
MeSH terms
Glucagon-Like Peptide-1 Receptor, Heart Disease Risk Factors, Glucagon-Like Peptide-1 Receptor Agonists, Clinical Trials as Topic, Heart Failure, Humans, Obesity, Risk Factors, Weight Loss, Treatment Outcome, Risk Assessment, Anti-Obesity Agents, Adiposity, Incretins

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