Evidence map›GIP/GLP-1 & amylin agonists × body weight & composition›PMID 39566869›Full record

Trial reportJournal of the American College of Cardiology2025

Tirzepatide Reduces LV Mass and Paracardiac Adipose Tissue in Obesity-Related Heart Failure: SUMMIT CMR Substudy.

Christopher M Kramer, Barry A Borlaug, Michael R Zile, Dustin Ruff, Joseph M DiMaria, Venu Menon, Yang Ou, Angela M Zarante, Karla C Hurt, Masahiro Murakami and 2 more

2 registry-linked trialsAbstract readRandomized Controlled TrialMulticenter Study
PubMed Publisher
In one paragraph

Trial report in Journal of the American College of Cardiology, 2025. The graph read 1 number from its abstract, feeding 1 cell of the map, but it casts no vote: it is a later paper about NCT04847557, whose primary report (PMID 39555826) speaks for the trial. It reports registered trial NCT04847557. Cited by 99 papers, 1 of them a synthesis that pooled it.

1number the graph read from it
0cells of the map it votes in
99citing papers in PubMed, 1 pooled it
–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.

← favours the treatmentfavours the comparator →
-69.00 · no effect
Body weight & compositionfavours the treatment · against placebo · obesity, heart_failurefeeds one cell of the map
decrease -45.0-69.0 to -22.0P < 0.001
Paracardiac adipose tissue decreased in the treated group by 45 mL (95% CI: -69 to -22 mL) when corrected for placebo (P < 0.001).
FeedsGIP/GLP-1 & amylin agonists×body weight & composition

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

GIP/GLP-1 & amylin agonists×body weight & composition

Does not voteOpen on the map →What to test next →

28 readable studies in this cell: 27 favour the treatment, 1 find no difference, 0 favour the comparator.

Belief with this paper
1.00replicated · 19 families support, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
This paper’s trial, registry resultNCT04847557 · 731 enrolled · 2021
Δ -11.6-12.8 to -10.4
Coadministered Cagrilintide and Semaglutide in Adults with Overweight …PMID 40544433 · 3,400 enrolled · 2022
Δ -17.3-18.1 to -16.6
NCT041846222,539 enrolled · 2019
Δ -13.5-14.6 to -12.5
NCT037306622,002 enrolled · 2018
Δ -9.00-9.80 to -8.30
NCT039879191,879 enrolled · 2019
Δ -1.70-2.60 to -0.70
NCT038829701,444 enrolled · 2019
Δ -9.80-10.8 to -8.80
NCT045379231,428 enrolled · 2020
Δ -10.7-11.5 to -9.90
Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type…PMID 40544432 · 1,200 enrolled · 2023
Δ -10.4-11.2 to -9.50
NCT04657003938 enrolled · 2021
Δ -10.1-11.5 to -8.80
NCT04093752917 enrolled · 2019
Δ -6.50-7.40 to -5.60
NCT04660643783 enrolled · 2021
Δ -21.4-22.9 to -20.0
NCT05822830751 enrolled · 2023
Δ -6.50-8.10 to -4.90
NCT03861052636 enrolled · 2019
Δ -5.20-6.40 to -4.10
4 · 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.

NCT04847557 phase3completed

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study Comparing the Efficacy and Safety of Tirzepatide Versus Placebo in Patients With Heart Failure With Preserved Ejection Fraction and Obesity (SUMMIT)

Ran2021Enrolled731Registered outcomes11Posted comparisons11ConditionsHeart Failure With Preserved Ejection Fraction (HFpEF), ObesityArmsPlacebo, Tirzepatide
Open the trial in the graph
NCT07567378 not yet recruitingstarted 2026, after this paper: background citation

Cartilage, Arthropathy and Imaging Under Tirzepatide in Zone-stratified Cohorts (CARTIZ): A Prospective Observational Multi-Institutional Registry of the VAT-Articular-Cardiac-Aging Axis in Adults Exposed to Tirzepatide in Mexico, With Quantitative Knee Cartilage T2 Mapping, Cardiac CT Epicardial Adipose Tissue Radiomic Phenotyping, HLA Stratification, Longitudinal Multi-Frequency Bioimpedance Body Composition, and a Prespecified Surgical Tissue Acquisition Subcohort

Ran2026Enrolled30Registered outcomes14Posted comparisons0ConditionsAtrial Fibrillation (AF), Coronary Artery Disease, Diabetes (DM), Heart FailureArmsTirzepatide
PMID 41406444PMID 40903131PMID 41666927PMID 38878772PMID 28701474PMID 41928037PMID 41944220PMID 42010357PMID 32154773PMID 30170852PMID 41903163other papers from this trial
Open the trial in the graph
5 · Its place in the literature

Who cites it

99 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Prognostic value of epicardial and pericardial adipose tissue in patients with chronic heart failure.Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation · 2026
    Article
  4. Review
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  7. Review
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  10. Review
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  18. Observational
  19. Review
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39 more citing papers are in PubMed but not listed here.

6 · The record

Corrections and comments

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

7 · Who and what money

Authors and funding

12 authors.

Christopher M KramerCardiovascular Division, Department of Medicine, University of Virginia Health, Charlottesville, Virginia, USA. Electronic address: ckramer@virginia.edu.
Barry A BorlaugDepartment of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Michael R ZileMedical University of South Carolina, Charleston, South Carolina, USA.
Dustin RuffEli Lilly and Company, Indianapolis, Indiana, USA.
Joseph M DiMariaCardiovascular Division, Department of Medicine, University of Virginia Health, Charlottesville, Virginia, USA.
Venu MenonDepartment of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA.
Yang OuEli Lilly and Company, Indianapolis, Indiana, USA.
Angela M ZaranteCINME S.A., Buenos Aires, Argentina.
Karla C HurtEli Lilly and Company, Indianapolis, Indiana, USA.
Masahiro MurakamiEli Lilly and Company, Indianapolis, Indiana, USA.
Milton PackerBaylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas, USA; Imperial College London, London, United Kingdom.
SUMMIT Trial Study Group

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

backgroundObesity is a known risk factor for heart failure with preserved ejection fraction (HFpEF) and is considered a distinct phenotype with more concentric remodeling. Epicardial adipose tissue (EAT) is also increased in obesity-related HFpEF and is associated with adverse events.

objectivesThe cardiac magnetic resonance (CMR) substudy of the SUMMIT trial aimed to examine the effects of tirzepatide on cardiac structure and function with the underlying hypothesis that it would reduce left ventricular (LV) mass and EAT in obesity-related HFpEF.

methodsA total of 175 patients with obesity-related HFpEF from the parent study of tirzepatide (2.5 mg subcutaneously weekly, increasing to a maximum of 15 mg weekly) or matching placebo underwent CMR at baseline, which consisted of multiplanar cine imaging. A total of 106 patients completed the CMR and had adequate image quality for analysis of LV and left atrial structure and function and paracardiac (epicardial plus pericardial) adipose tissue at both baseline and 52 weeks. The prespecified primary endpoint of this substudy was between-group changes in LV mass.

resultsLV mass decreased by 11 g (95% CI: -19 to -4 g) in the treated group (n = 50) when corrected for placebo (n = 56) (P = 0.004). Paracardiac adipose tissue decreased in the treated group by 45 mL (95% CI: -69 to -22 mL) when corrected for placebo (P < 0.001). The change in LV mass in the treated group correlated with changes in body weight (P < 0.02) and tended to correlate with changes in waist circumference and blood pressure (P = 0.06 for both). The LV mass change also correlated with changes in LV end-diastolic volume and left atrial end-diastolic and end-systolic volumes (P < 0.03 for all).

conclusionsThe CMR substudy of the SUMMIT trial demonstrated that tirzepatide therapy in obesity-related HFpEF led to reduced LV mass and paracardiac adipose tissue as compared with placebo, and the change in LV mass paralleled weight loss. These physiologic changes may contribute to the reduction in heart failure events seen in the main SUMMIT trial. (A Study of Tirzepatide [LY3298176] in Participants With Heart Failure With Preserved Ejection Fraction [HFpEF] and Obesity: The SUMMIT Trial; NCT04847557).

Indexed as

Adipose TissueHeart FailureHeart VentriclesObesityAgedDouble-Blind MethodFemaleHumansMagnetic Resonance Imaging, CineMaleMiddle AgedStroke VolumeTirzepatideTirzepatidecardiac MRIGLP1 agonistHFpEFLV massobesity

Identifiers

PMID39566869

What OpenQuestion holds

Texttitle and abstract
Read underepoch 390

Registered trials

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 OpenQuestion graph.