Evidence mapPaperPMID 41256540Full record

ArticlebioRxiv : the preprint server for biology2025

Low Dose GLP-1 Therapy Attenuates Pathological Cardiac and Hepatic Remodelling in HFpEF Independent of Weight Loss.

Mahmoud H Elbatreek, Zhen Li, Xiaoman Yu, Natalie D Gehred, Tatiana Gromova, Jingshu Chen, Naoto Muraoka, Martin Jensen, Vinay Kartha, Chris Carrico and 11 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Mahmoud H ElbatreekDepartment of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA.ORCID 0000-0003-2437-1773
Zhen LiSchool of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China.
Xiaoman YuSchool of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China.
Natalie D GehredDepartments of Anesthesiology & Perioperative Medicine, Medicine and Physiology, Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, CA.
Tatiana GromovaDepartments of Anesthesiology & Perioperative Medicine, Medicine and Physiology, Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, CA.
Jingshu ChenGordian Biotechnology, South San Francisco, CA.
Naoto MuraokaGordian Biotechnology, South San Francisco, CA.
Martin JensenGordian Biotechnology, South San Francisco, CA.
Vinay KarthaGordian Biotechnology, South San Francisco, CA.
Chris CarricoGordian Biotechnology, South San Francisco, CA.
Timothy D AllertonVascular Metabolism Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA.
Michael E BowdishDepartment of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
Joanna ChikweDepartment of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
Sanjiv J ShahNorthwestern University Medicine, Feinberg School of Medicine, Chicago, IL.
Kathleen C WoulfeDepartment of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora.
Timothy A McKinseyDepartment of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora.
Edwin YooDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
David J PolhemusDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Thomas M VondriskaDepartments of Anesthesiology & Perioperative Medicine, Medicine and Physiology, Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, CA.
Traci T GoodchildDepartment of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
David J LeferDepartment of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA.

Funding

Hydrogen Sulfide and GLP-1 Combination Therapy to Treat HFpEFR01HL181016 · CEDARS-SINAI MEDICAL CENTER · 2025 to 2025
$759k
Epigenetic Regulation of Heart Failure with Preserved Ejection FractionR01HL174996 · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2025 to 2025
$699k
Dynamics of cardiac nuclei in heart diseaseR01HL105699 · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2025 to 2025
$390k
NHLBI NIH HHS R01 HL105699NHLBI NIH HHS R01 HL159428NHLBI NIH HHS R01 HL174996NHLBI NIH HHS R01 HL181016
6 · The paper itself

Abstract

BACKGROUND AND

aimsHeart failure with preserved ejection fraction (HFpEF) remains a therapeutic challenge. GLP-1 receptor agonists (GLP-1RAs) show clinical promise, and the prevailing hypothesis is that their benefits are primarily driven by weight loss and the downstream benefits of improved functional status. We investigated the weight loss-independent effects of low-dose GLP-1RA therapy in a clinically relevant rodent model of severe cardiometabolic HFpEF.

methodsTen-week-old male ZSF1 obese rats with spontaneous HFpEF were treated with low-dose semaglutide (30 nmol/kg twice weekly, n=6) or vehicle for 16 weeks. Comprehensive assessments included body weight, 2-D echocardiography, invasive hemodynamics, exercise capacity as well as cardiac and hepatic fibrosis and lipid deposition. The study utilized advanced multi-omics approaches, including single-cell RNA sequencing of the heart and liver, as well as cardiac, hepatic and plasma proteomics, to explore underlying mechanisms.

resultsIn ZSF1 obese rats, low-dose semaglutide in the absence of weight loss, significantly improved cardiac function, exercise tolerance, and attenuated fibrosis in the heart and liver. Interestingly, semaglutide therapy reduced cardiac and hepatic lipid content as well as lipid droplets in cardiac myocytes and hepatocytes. Mechanistically, multi-omics analyses of cardiac and hepatic tissues revealed that semaglutide exerted these benefits by improving cardiac metabolism, interfering with pro-fibrotic and pro-hypertrophic signals, and by reducing systemic inflammation.

conclusionsLow-dose semaglutide provides significant cardioprotective, hepatoprotective, and metabolic benefits in HFpEF independent of weight loss. Our findings support the investigation of lower GLP-1RA dosing in HFpEF and other cardiovascular conditions, including in non-obese patients, to expand the clinical utility of these potent drugs.

Indexed as

BCAAFibrosisGLP-1HFpEFSemaglutideZSF1 Obese Rats

Identifiers

PMID41256540
PMCPMC12621885

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.