Impact of Body Mass Index, Central Adiposity, and Weight Loss on the Benefits of Tirzepatide in HFpEF: The SUMMIT Trial.

Borlaug BA, Zile MR, Kramer CM, Ye W, Ou Y, Hurt K, Murakami M, Packer M

Journal of the American College of Cardiology1 Jul 2025Cited by 27 (Europe PMC)

PMID40701669DOI10.1016/j.jacc.2025.04.059PepBankPUB-40701669

Publisher page PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study11

11 results from studies that gave the peptide. 11 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with obesity-related HFpEF, the effect of tirzepatide on worsening heart failure or cardiovascular death did not differ by baseline BMI or waist-height ratio tertile.
In plain wordsIn adults with obesity and heart failure, tirzepatide lowered heart failure risk to a similar degree whatever the starting BMI or waist size.
Peptide
Tirzepatide
Outcome
No significant changeRisk of worsening heart failure or cardiovascular death by BMI and WHR tertile
Study
n = 731
Comparator
Placebo
Analysis
Primary
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated · 52 weeksAs given in this study (human).
Source sentences
Summary
There was no evidence of heterogeneity in the effect of tirzepatide on the risk of worsening HF or cardiovascular death by BMI or WHR tertile.
1 context sentence(design, population, supporting numbers)
Summary · context
In the SUMMIT trial, 731 patients with NYHA functional class II-IV HFpEF and body mass index (BMI) ≥30 kg/m² were randomly assigned to tirzepatide (n = 364) or placebo (n = 367).
Report a problemFND-4070166901
02HumanRandomized controlled trialEfficacy outcome
In adults with obesity-related HFpEF, there was a trend, not significant, for greater KCCQ-CSS improvement with tirzepatide in higher baseline BMI tertiles (P = 0.097).
In plain wordsIn adults with obesity and heart failure, the symptom score showed only a weak, non-significant trend to improve more with higher starting BMI.
Peptide
Tirzepatide
Outcome
No significant changeKCCQ-CSS by BMI tertile
Study
n = 731
Comparator
Placebo
Analysis
Primary
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated · 52 weeksAs given in this study (human).
Source sentences
Summary
with a trend for greater improvement in KCCQ-CSS (P = 0.097).
1 context sentence(design, population, supporting numbers)
Summary · context
In the SUMMIT trial, 731 patients with NYHA functional class II-IV HFpEF and body mass index (BMI) ≥30 kg/m² were randomly assigned to tirzepatide (n = 364) or placebo (n = 367).
Report a problemFND-4070166905
03HumanRandomized controlled trialEfficacy outcome
In adults with obesity-related HFpEF, tirzepatide improved 6-minute walk distance more than placebo, with larger gains in higher baseline BMI tertiles (ETD 9.9 vs 26.3 vs 37.5 m).
In plain wordsIn adults with obesity and heart failure, tirzepatide improved walking distance more than placebo, and more so in those with higher starting BMI.
Peptide
Tirzepatide
Outcome
Increase6-minute walk distance by BMI tertile
Study
n = 731
Comparator
Placebo
Analysis
Secondary
Outcome group
Exercise and physical function · Cardiovascular
Studied dose
Dose not stated · 52 weeksAs given in this study (human).
Measurements
ETD 6MWD
9.9 m
lowest BMI tertile
ETD 6MWD
26.3 m
middle BMI tertile
ETD 6MWD
37.5 m
highest BMI tertile
Source sentences
Summary
greater improvements in 6MWD (estimated treatment difference [ETD]: 9.9 vs 26.3 vs 37.5 m; P = 0.025)
1 context sentence(design, population, supporting numbers)
Summary · context
In the SUMMIT trial, 731 patients with NYHA functional class II-IV HFpEF and body mass index (BMI) ≥30 kg/m² were randomly assigned to tirzepatide (n = 364) or placebo (n = 367).
Report a problemFND-4070166902
04HumanRandomized controlled trialEfficacy outcome
In adults with obesity-related HFpEF, tirzepatide reduced body weight more than placebo, with larger decreases in higher baseline BMI tertiles (ETD -10.7% vs -11.8% vs -14.4%).
In plain wordsIn adults with obesity and heart failure, tirzepatide cut body weight more than placebo, and more so in those with higher starting BMI.
Peptide
Tirzepatide
Outcome
DecreaseBody weight change by BMI tertile
Study
n = 731
Comparator
Placebo
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · 52 weeksAs given in this study (human).
Measurements
ETD body weight
−10.7%
lowest BMI tertile
ETD body weight
−11.8%
middle BMI tertile
ETD body weight
−14.4%
highest BMI tertile
Source sentences
Summary
greater decreases in BW (ETD: -10.7% vs -11.8% vs -14.4%; P = 0.006)
1 context sentence(design, population, supporting numbers)
Summary · context
In the SUMMIT trial, 731 patients with NYHA functional class II-IV HFpEF and body mass index (BMI) ≥30 kg/m² were randomly assigned to tirzepatide (n = 364) or placebo (n = 367).
Report a problemFND-4070166903
05HumanRandomized controlled trialEfficacy outcome
In adults with obesity-related HFpEF, tirzepatide lowered systolic blood pressure more than placebo, with larger decreases in higher baseline BMI tertiles (ETD -1.00 vs -6.65 vs -6.62 mm Hg).
In plain wordsIn adults with obesity and heart failure, tirzepatide lowered systolic blood pressure more than placebo, more so with higher starting BMI.
Peptide
Tirzepatide
Outcome
DecreaseSystolic blood pressure by BMI tertile
Study
n = 731
Comparator
Placebo
Outcome group
Blood pressure · Cardiovascular
Studied dose
Dose not stated · 52 weeksAs given in this study (human).
Measurements
ETD systolic blood pressure
−1 mm Hg
lowest BMI tertile
ETD systolic blood pressure
−6.65 mm Hg
middle BMI tertile
ETD systolic blood pressure
−6.62 mm Hg
highest BMI tertile
Source sentences
Summary
systolic blood pressure (ETD: -1.00 vs -6.65 vs -6.62 mm Hg; P = 0.035)
1 context sentence(design, population, supporting numbers)
Summary · context
In the SUMMIT trial, 731 patients with NYHA functional class II-IV HFpEF and body mass index (BMI) ≥30 kg/m² were randomly assigned to tirzepatide (n = 364) or placebo (n = 367).
Report a problemFND-4070166904
06HumanObservational studyMechanism
Among tirzepatide-treated adults with obesity-related HFpEF, greater weight loss at 52 weeks was associated with larger improvements in 6-minute walk distance.
In plain wordsAmong people with obesity and heart failure on tirzepatide, more weight loss was linked to a bigger gain in walking distance.
Peptide
Tirzepatide
Outcome
Not applicableWeight loss and change in 6-minute walk distance
Study
n = 364
Outcome group
Exercise and physical function · Cardiovascular
Studied dose
Dose not stated · 52 weeksAs given in this study (human).
Source sentences
Summary
Among those randomized to tirzepatide, greater weight loss at 52 weeks was associated with larger improvements in 6MWD, KCCQ-CSS, CRP, and blood pressure
1 context sentence(design, population, supporting numbers)
Summary · context
In the SUMMIT trial, 731 patients with NYHA functional class II-IV HFpEF and body mass index (BMI) ≥30 kg/m² were randomly assigned to tirzepatide (n = 364) or placebo (n = 367).
Report a problemFND-4070166906
07HumanObservational studyMechanism
Among tirzepatide-treated adults with obesity-related HFpEF, greater weight loss at 52 weeks was associated with larger improvements in KCCQ-CSS.
In plain wordsAmong people with obesity and heart failure on tirzepatide, more weight loss was linked to a bigger gain in the heart failure symptom score.
Peptide
Tirzepatide
Outcome
Not applicableWeight loss and change in KCCQ-CSS
Study
n = 364
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated · 52 weeksAs given in this study (human).
Source sentences
Summary
Among those randomized to tirzepatide, greater weight loss at 52 weeks was associated with larger improvements in 6MWD, KCCQ-CSS, CRP, and blood pressure
1 context sentence(design, population, supporting numbers)
Summary · context
In the SUMMIT trial, 731 patients with NYHA functional class II-IV HFpEF and body mass index (BMI) ≥30 kg/m² were randomly assigned to tirzepatide (n = 364) or placebo (n = 367).
Report a problemFND-4070166907
08HumanObservational studyMechanism
Among tirzepatide-treated adults with obesity-related HFpEF, greater weight loss at 52 weeks was associated with larger improvements in CRP.
In plain wordsAmong people with obesity and heart failure on tirzepatide, more weight loss was linked to a bigger fall in an inflammation marker.
Peptide
Tirzepatide
Outcome
Not applicableWeight loss and change in CRP
Study
n = 364
Outcome group
Inflammation markers · Cardiovascular
Studied dose
Dose not stated · 52 weeksAs given in this study (human).
Source sentences
Summary
Among those randomized to tirzepatide, greater weight loss at 52 weeks was associated with larger improvements in 6MWD, KCCQ-CSS, CRP, and blood pressure
1 context sentence(design, population, supporting numbers)
Summary · context
In the SUMMIT trial, 731 patients with NYHA functional class II-IV HFpEF and body mass index (BMI) ≥30 kg/m² were randomly assigned to tirzepatide (n = 364) or placebo (n = 367).
Report a problemFND-4070166908
09HumanObservational studyMechanism
Among tirzepatide-treated adults with obesity-related HFpEF, greater weight loss at 52 weeks was associated with larger improvements in blood pressure.
In plain wordsAmong people with obesity and heart failure on tirzepatide, more weight loss was linked to a bigger fall in blood pressure.
Peptide
Tirzepatide
Outcome
Not applicableWeight loss and change in blood pressure
Study
n = 364
Outcome group
Blood pressure · Cardiovascular
Studied dose
Dose not stated · 52 weeksAs given in this study (human).
Source sentences
Summary
Among those randomized to tirzepatide, greater weight loss at 52 weeks was associated with larger improvements in 6MWD, KCCQ-CSS, CRP, and blood pressure
1 context sentence(design, population, supporting numbers)
Summary · context
In the SUMMIT trial, 731 patients with NYHA functional class II-IV HFpEF and body mass index (BMI) ≥30 kg/m² were randomly assigned to tirzepatide (n = 364) or placebo (n = 367).
Report a problemFND-4070166909
10HumanObservational studyMechanism
Among tirzepatide-treated adults with obesity-related HFpEF, a greater decrease in waist circumference was associated with larger increases in 6-minute walk distance.
In plain wordsAmong people with obesity and heart failure on tirzepatide, a bigger fall in waist size was linked to a bigger gain in walking distance.
Peptide
Tirzepatide
Outcome
Not applicableWaist circumference decrease and change in 6-minute walk distance
Study
n = 364
Outcome group
Exercise and physical function · Cardiovascular
Studied dose
Dose not stated · 52 weeksAs given in this study (human).
Source sentences
Summary
a greater decrease in WC was associated with larger increases in 6MWD and KCCQ-CSS.
1 context sentence(design, population, supporting numbers)
Summary · context
In the SUMMIT trial, 731 patients with NYHA functional class II-IV HFpEF and body mass index (BMI) ≥30 kg/m² were randomly assigned to tirzepatide (n = 364) or placebo (n = 367).
Report a problemFND-4070166910
11HumanObservational studyMechanism
Among tirzepatide-treated adults with obesity-related HFpEF, a greater decrease in waist circumference was associated with larger increases in KCCQ-CSS.
In plain wordsAmong people with obesity and heart failure on tirzepatide, a bigger fall in waist size was linked to a bigger gain in the symptom score.
Peptide
Tirzepatide
Outcome
Not applicableWaist circumference decrease and change in KCCQ-CSS
Study
n = 364
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated · 52 weeksAs given in this study (human).
Source sentences
Summary
a greater decrease in WC was associated with larger increases in 6MWD and KCCQ-CSS.
1 context sentence(design, population, supporting numbers)
Summary · context
In the SUMMIT trial, 731 patients with NYHA functional class II-IV HFpEF and body mass index (BMI) ≥30 kg/m² were randomly assigned to tirzepatide (n = 364) or placebo (n = 367).
Report a problemFND-4070166911

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT04847557

A Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) and Obesity: The SUMMIT Trial

Eli Lilly and Companyn = 73120 Apr 2021 to 2 Jul 2024

Obesity · Heart Failure With Preserved Ejection Fraction (HFpEF)

Trial page ClinicalTrials.govUpdated 20 Aug 2025

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
12 Oct 2026, 12:58 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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