Evidence mapPaperPMID 42417681Full record

ArticleJACC. Heart failure2026

Effects of Tirzepatide in Obesity-Related HFpEF by Sex: A Prespecified Secondary Analysis From the SUMMIT Trial.

Barry A Borlaug, Michael R Zile, Christopher M Kramer, Sheldon E Litwin, Wenyu Ye, Yang Ou, Karla Hurt, Masahiro Murakami, Milton Packer, SUMMIT Trial Group

Registry-linked trialAbstract read
In one paragraph

Article in JACC. Heart failure, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT04847557. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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.

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
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Barry A BorlaugDepartment of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA. Electronic address: borlaug.barry@mayo.edu.
Michael R ZileDivision of Cardiology, Medical University of South Carolina and the Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina, USA.
Christopher M KramerCardiovascular Division, Department of Medicine, and Department of Radiology and Medical Imaging, University of Virginia Health, Charlottesville, Virginia, USA.
Sheldon E LitwinDivision of Cardiology, Medical University of South Carolina and the Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina, USA.
Wenyu YeEli Lilly and Company, Indianapolis, Indiana, USA.
Yang OuEli Lilly and Company, Indianapolis, Indiana, USA.
Karla HurtEli Lilly and Company, Indianapolis, Indiana, USA.
Masahiro MurakamiEli Lilly and Company, Indianapolis, Indiana, USA.
Milton PackerBaylor University Medical Center, Dallas, Texas, USA; Imperial College, London, United Kingdom.
SUMMIT Trial Group

Funding

Pulmonary Hypertension in Left Heart DiseaseR01HL162828 · MAYO CLINIC ROCHESTER · 2025 to 2025
$790k
Mayo Clinic HeartShare Clinical CenterU01HL160226 · MAYO CLINIC ROCHESTER · 2025 to 2025
$281k
NHLBI NIH HHS R01 HL162828NHLBI NIH HHS U01 HL160226
6 · The paper itself

Abstract

backgroundThe SUMMIT trial showed that the long-acting glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist tirzepatide decreased risk of cardiovascular death or worsening heart failure (HF) in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Women outnumber men with HFpEF, and there are sexual dimorphisms in the relationships between body fat and pathophysiology that could influence response to tirzepatide.

objectivesThis study aims to compare baseline characteristics and effects of tirzepatide on primary and other endpoints in women and men with obesity-related HFpEF.

methodsIn the SUMMIT trial, 731 patients with NYHA functional class II-IV HFpEF and body mass index (BMI) ≥30 kg/m

resultsCompared with men (n = 338, 46.2%), women with obesity-related HFpEF (n = 393, 53.8%) had greater BMI, waist to height ratio (WHtR), symptom severity (higher NYHA functional class, lower KCCQ-CSS), and poorer exercise capacity (lower 6MWD), whereas men had greater left ventricular remodeling and paracardiac fat. Greater baseline BMI or WHtR were correlated with lower KCCQ-CSS and 6MWD in women and men, with no interaction, but higher WHtR was associated with poorer kidney function exclusively in women (interaction P = 0.043). The effect of tirzepatide on the risk of worsening HF or cardiovascular death did not differ in women and men (HR: 0.66 and 0.61, respectively, interaction P = 0.81), with no heterogeneity of effect on KCCQ-CSS at 52 weeks (8.1- and 5.5-point placebo-corrected improvement, respectively, interaction P = 0.43) or 6MWD (18 m and 15 m placebo-corrected improvement, respectively, interaction P = 0.76). Among patients randomized to tirzepatide, decreases in body weight on treatment were more strongly associated with improvements in KCCQ-CSS in women than men (interaction P = 0.0058).

conclusionsCompared with men, women with obesity-related HFpEF have greater adiposity, symptom severity, and poorer exercise capacity but lower left ventricular mass and paracardiac fat deposition. Despite these differences, tirzepatide resulted in consistent benefits across multiple domains of HF severity that did not differ by sex. (A Study of Tirzepatide [LY3291876] in Participation With Heart Failure With Preserved Ejection Fraction [HFpEF] and Obesity [SUMMIT]; NCT04847557).

Indexed as

clinical trialheart failureheart failure with preserved ejection fractionobesitypathophysiologysex differencestirzepatidewomen

Identifiers

PMID42417681
PMCPMC13398731

What Socratic holds

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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 Socratic graph.