Influence of Type 2 Diabetes on the Effects of Tirzepatide in Patients With Heart Failure and a Preserved Ejection Fraction With Obesity: A Prespecified Stratification-Based Analysis.

Packer M, Zile MR, Kramer CM, DiMaria JM, Baum SJ, Litwin SE, Murakami M, Zhou C, Ou Y, Koeneman L, Borlaug BA

Journal of the American College of Cardiology1 Sept 2025Cited by 11 (Europe PMC)

PMID40903131DOI10.1016/j.jacc.2025.06.058PepBankPUB-40903131

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: CC BY-NC-ND. Results still quote short attributed sentences.

Results from this study14

14 results from studies that gave the peptide. 14 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with HFpEF and obesity, cardiovascular death or worsening heart failure events occurred less often with tirzepatide than with placebo (HR 0.62).
In plain wordsIn adults with heart failure and obesity, tirzepatide led to fewer cardiovascular deaths or worsening heart failure events than placebo.
Peptide
Tirzepatide
Outcome
DecreaseCardiovascular death or worsening heart failure event
Study
n = 731
Comparator
Placebo
Analysis
Primary
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
up to 15 mg · subcutaneous · median 104 weeksAs given in this study (human).
Measurements
Hazard ratio
0.62
overall
Source sentences
Summary
Overall, cardiovascular death or worsening heart failure events occurred less frequently in the tirzepatide group (HR: 0.62; 95% CI: 0.41-0.95; P = 0.026), primarily related to fewer worsening heart failure events.
1 context sentence(design, population, supporting numbers)
Summary · context
In a double-blind trial, 731 patients with heart failure and a preserved ejection fraction (HFpEF) with a body mass index ≥30 kg/m² were randomly assigned in a 1:1 ratio to receive tirzepatide (up to 15 mg subcutaneously weekly) or placebo for a median of 104 weeks.
Report a problemFND-4090313101
02HumanRandomized controlled trialEfficacy outcome
In adults with HFpEF and obesity, tirzepatide improved the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score significantly.
In plain wordsIn adults with heart failure and obesity, tirzepatide improved the heart failure symptom and quality-of-life score compared with placebo.
Peptide
Tirzepatide
Outcome
IncreaseKCCQ Clinical Summary Score improvement
Study
n = 731
Comparator
Placebo
Analysis
Primary
Outcome group
Quality of life · Cardiovascular
Studied dose
up to 15 mg · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
The magnitude of the improvement in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, 6-minute walk distance, quality-of-life scores, and NYHA functional class with tirzepatide was statistically significant
1 context sentence(design, population, supporting numbers)
Summary · context
In a double-blind trial, 731 patients with heart failure and a preserved ejection fraction (HFpEF) with a body mass index ≥30 kg/m² were randomly assigned in a 1:1 ratio to receive tirzepatide (up to 15 mg subcutaneously weekly) or placebo for a median of 104 weeks.
Report a problemFND-4090313105
03HumanRandomized controlled trialEfficacy outcome
In adults with HFpEF and obesity, the tirzepatide effect on cardiovascular death or worsening heart failure was similar with and without diabetes (P interaction = 0.95).
In plain wordsIn adults with heart failure and obesity, tirzepatide worked similarly on heart failure events whether or not they had diabetes.
Peptide
Tirzepatide
Outcome
No significant changeEffect on cardiovascular death or worsening heart failure by diabetes status
Study
n = 731
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
up to 15 mg · subcutaneous · median 104 weeksAs given in this study (human).
Source sentences
Summary
The effect in patients with or without diabetes was similar: HR of 0.64 (95% CI: 0.35-1.15) in patients with diabetes and 0.61 (95% CI: 0.33-1.10) in patients without diabetes (P_interaction = 0.95).
1 context sentence(design, population, supporting numbers)
Summary · context
In a double-blind trial, 731 patients with heart failure and a preserved ejection fraction (HFpEF) with a body mass index ≥30 kg/m² were randomly assigned in a 1:1 ratio to receive tirzepatide (up to 15 mg subcutaneously weekly) or placebo for a median of 104 weeks.
Report a problemFND-4090313104
04HumanRandomized controlled trialEfficacy outcome
In adults with HFpEF and obesity, tirzepatide significantly improved 6-minute walk distance.
In plain wordsIn adults with heart failure and obesity, tirzepatide improved walking distance in 6 minutes compared with placebo.
Peptide
Tirzepatide
Outcome
Increase6-minute walk distance improvement
Study
n = 731
Comparator
Placebo
Outcome group
Exercise and physical function · Cardiovascular
Studied dose
up to 15 mg · subcutaneous · median 104 weeksAs given in this study (human).
Source sentences
Summary
The magnitude of the improvement in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, 6-minute walk distance, quality-of-life scores, and NYHA functional class with tirzepatide was statistically significant
1 context sentence(design, population, supporting numbers)
Summary · context
In a double-blind trial, 731 patients with heart failure and a preserved ejection fraction (HFpEF) with a body mass index ≥30 kg/m² were randomly assigned in a 1:1 ratio to receive tirzepatide (up to 15 mg subcutaneously weekly) or placebo for a median of 104 weeks.
Report a problemFND-4090313106
05HumanRandomized controlled trialEfficacy outcome
In adults with HFpEF and obesity, tirzepatide significantly improved quality-of-life scores.
In plain wordsIn adults with heart failure and obesity, tirzepatide improved quality-of-life scores compared with placebo.
Peptide
Tirzepatide
Outcome
IncreaseQuality-of-life scores improvement
Study
n = 731
Comparator
Placebo
Outcome group
Quality of life · Cardiovascular
Studied dose
up to 15 mg · subcutaneous · median 104 weeksAs given in this study (human).
Source sentences
Summary
The magnitude of the improvement in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, 6-minute walk distance, quality-of-life scores, and NYHA functional class with tirzepatide was statistically significant
1 context sentence(design, population, supporting numbers)
Summary · context
In a double-blind trial, 731 patients with heart failure and a preserved ejection fraction (HFpEF) with a body mass index ≥30 kg/m² were randomly assigned in a 1:1 ratio to receive tirzepatide (up to 15 mg subcutaneously weekly) or placebo for a median of 104 weeks.
Report a problemFND-4090313107
06HumanRandomized controlled trialEfficacy outcome
In adults with HFpEF and obesity, tirzepatide significantly improved NYHA functional class.
In plain wordsIn adults with heart failure and obesity, tirzepatide improved heart failure functional class compared with placebo.
Peptide
Tirzepatide
Outcome
Not applicableNYHA functional class improvement
Study
n = 731
Comparator
Placebo
Outcome group
Heart function · Cardiovascular
Studied dose
up to 15 mg · subcutaneous · median 104 weeksAs given in this study (human).
Source sentences
Summary
The magnitude of the improvement in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, 6-minute walk distance, quality-of-life scores, and NYHA functional class with tirzepatide was statistically significant
1 context sentence(design, population, supporting numbers)
Summary · context
In a double-blind trial, 731 patients with heart failure and a preserved ejection fraction (HFpEF) with a body mass index ≥30 kg/m² were randomly assigned in a 1:1 ratio to receive tirzepatide (up to 15 mg subcutaneously weekly) or placebo for a median of 104 weeks.
Report a problemFND-4090313108
07HumanRandomized controlled trialEfficacy outcome
In adults with HFpEF and obesity, the tirzepatide improvements in symptom score, walk distance, quality of life and NYHA class did not differ between patients with and without type 2 diabetes.
In plain wordsIn adults with heart failure and obesity, tirzepatide improved symptoms and function to a similar degree with or without diabetes.
Peptide
Tirzepatide
Outcome
No significant changeImprovement in KCCQ, 6-minute walk, quality of life and NYHA class by diabetes status
Study
n = 731
Comparator
Patients without type 2 diabetes
Outcome group
Quality of life · Cardiovascular
Studied dose
up to 15 mg · subcutaneous · median 104 weeksAs given in this study (human).
Source sentences
Summary
did not differ in patients with and without type 2 diabetes.
1 context sentence(design, population, supporting numbers)
Summary · context
In a double-blind trial, 731 patients with heart failure and a preserved ejection fraction (HFpEF) with a body mass index ≥30 kg/m² were randomly assigned in a 1:1 ratio to receive tirzepatide (up to 15 mg subcutaneously weekly) or placebo for a median of 104 weeks.
Report a problemFND-4090313109
08HumanRandomized controlled trialEfficacy outcome
In adults with HFpEF and obesity, tirzepatide weight loss at 52 weeks was less pronounced in patients with type 2 diabetes than in those without (P interaction = 0.04).
In plain wordsIn adults with heart failure and obesity, tirzepatide led to less weight loss in people with diabetes than in people without diabetes.
Peptide
Tirzepatide
Outcome
Not applicableWeight loss at 52 weeks, diabetes versus no diabetes
Study
n = 731
Comparator
Patients without type 2 diabetes
Outcome group
Body weight · Metabolic and weight
Studied dose
up to 15 mg · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
At 52 weeks, weight loss was less pronounced in patients with type 2 diabetes; patients with diabetes lost 10.4% (95% CI: 8.7%-12.2%) of body weight, compared with 12.9% (95% CI: 11.2%-14.6%) in patients without diabetes (P_interaction = 0.04).
1 context sentence(design, population, supporting numbers)
Summary · context
In a double-blind trial, 731 patients with heart failure and a preserved ejection fraction (HFpEF) with a body mass index ≥30 kg/m² were randomly assigned in a 1:1 ratio to receive tirzepatide (up to 15 mg subcutaneously weekly) or placebo for a median of 104 weeks.
Report a problemFND-4090313112
09HumanRandomized controlled trialEfficacy outcome
In adults with HFpEF, obesity and type 2 diabetes, the hazard ratio for cardiovascular death or worsening heart failure with tirzepatide was 0.64 (95% CI 0.35-1.15).
In plain wordsIn adults with heart failure, obesity and diabetes, tirzepatide showed a hazard ratio of 0.64 for heart failure events or cardiovascular death compared with placebo.
Peptide
Tirzepatide
Outcome
No significant changeCardiovascular death or worsening heart failure event in patients with diabetes
Study
n: not reported in source
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
up to 15 mg · subcutaneous · median 104 weeksAs given in this study (human).
Measurements
Hazard ratio
0.64
with diabetes
Source sentences
Summary
HR of 0.64 (95% CI: 0.35-1.15) in patients with diabetes
1 context sentence(design, population, supporting numbers)
Summary · context
In a double-blind trial, 731 patients with heart failure and a preserved ejection fraction (HFpEF) with a body mass index ≥30 kg/m² were randomly assigned in a 1:1 ratio to receive tirzepatide (up to 15 mg subcutaneously weekly) or placebo for a median of 104 weeks.
Report a problemFND-4090313102
10HumanRandomized controlled trialEfficacy outcome
In adults with HFpEF and obesity without type 2 diabetes, the hazard ratio for cardiovascular death or worsening heart failure with tirzepatide was 0.61 (95% CI 0.33-1.10).
In plain wordsIn adults with heart failure and obesity without diabetes, tirzepatide showed a hazard ratio of 0.61 for heart failure events or cardiovascular death versus placebo.
Peptide
Tirzepatide
Outcome
No significant changeCardiovascular death or worsening heart failure event in patients without diabetes
Study
n: not reported in source
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
up to 15 mg · subcutaneous · median 104 weeksAs given in this study (human).
Measurements
Hazard ratio
0.61
without diabetes
Source sentences
Summary
0.61 (95% CI: 0.33-1.10) in patients without diabetes
1 context sentence(design, population, supporting numbers)
Summary · context
In a double-blind trial, 731 patients with heart failure and a preserved ejection fraction (HFpEF) with a body mass index ≥30 kg/m² were randomly assigned in a 1:1 ratio to receive tirzepatide (up to 15 mg subcutaneously weekly) or placebo for a median of 104 weeks.
Report a problemFND-4090313103
11HumanRandomized controlled trialEfficacy outcome
In adults with HFpEF, obesity and type 2 diabetes, tirzepatide led to 10.4% body weight loss at 52 weeks.
In plain wordsIn adults with heart failure, obesity and diabetes, tirzepatide led to 10.4% body weight loss at 52 weeks.
Peptide
Tirzepatide
Outcome
DecreaseBody weight loss at 52 weeks in patients with type 2 diabetes
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Studied dose
up to 15 mg · subcutaneous · 52 weeksAs given in this study (human).
Measurements
Body weight loss
10.4%
with type 2 diabetes
Source sentences
Summary
patients with diabetes lost 10.4% (95% CI: 8.7%-12.2%) of body weight
1 context sentence(design, population, supporting numbers)
Summary · context
In a double-blind trial, 731 patients with heart failure and a preserved ejection fraction (HFpEF) with a body mass index ≥30 kg/m² were randomly assigned in a 1:1 ratio to receive tirzepatide (up to 15 mg subcutaneously weekly) or placebo for a median of 104 weeks.
Report a problemFND-4090313110
12HumanRandomized controlled trialEfficacy outcome
In adults with HFpEF and obesity without type 2 diabetes, tirzepatide led to 12.9% body weight loss at 52 weeks.
In plain wordsIn adults with heart failure and obesity without diabetes, tirzepatide led to 12.9% body weight loss at 52 weeks.
Peptide
Tirzepatide
Outcome
DecreaseBody weight loss at 52 weeks in patients without type 2 diabetes
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Studied dose
up to 15 mg · subcutaneous · 52 weeksAs given in this study (human).
Measurements
Body weight loss
12.9%
without type 2 diabetes
Source sentences
Summary
compared with 12.9% (95% CI: 11.2%-14.6%) in patients without diabetes
1 context sentence(design, population, supporting numbers)
Summary · context
In a double-blind trial, 731 patients with heart failure and a preserved ejection fraction (HFpEF) with a body mass index ≥30 kg/m² were randomly assigned in a 1:1 ratio to receive tirzepatide (up to 15 mg subcutaneously weekly) or placebo for a median of 104 weeks.
Report a problemFND-4090313111
13HumanRandomized controlled trialEfficacy outcome
In adults with HFpEF and obesity, tirzepatide reduced paracardiac fat, with similar decreases in patients with and without diabetes.
In plain wordsIn adults with heart failure and obesity, tirzepatide lowered fat around the heart, in people with and without diabetes alike.
Peptide
Tirzepatide
Outcome
DecreaseParacardiac fat change at 52 weeks
Study
n: not reported in source
Outcome group
Heart function · Cardiovascular
Studied dose
up to 15 mg · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
patients with or without diabetes showed similar decreases in visceral adiposity (as reflected by the decline in paracardiac fat
2 context sentences(design, population, supporting numbers)
Summary · context
Paired cardiac magnetic resonance imaging was used to assess changes in left ventricular mass and paracardiac fat at 52 weeks.
Summary · context
In a double-blind trial, 731 patients with heart failure and a preserved ejection fraction (HFpEF) with a body mass index ≥30 kg/m² were randomly assigned in a 1:1 ratio to receive tirzepatide (up to 15 mg subcutaneously weekly) or placebo for a median of 104 weeks.
Report a problemFND-4090313113
14HumanRandomized controlled trialEfficacy outcome
In adults with HFpEF and obesity, tirzepatide reduced left ventricular mass, with similar decreases in patients with and without diabetes.
In plain wordsIn adults with heart failure and obesity, tirzepatide lowered heart muscle mass, in people with and without diabetes alike.
Peptide
Tirzepatide
Outcome
DecreaseLeft ventricular mass change at 52 weeks
Study
n: not reported in source
Outcome group
Heart function · Cardiovascular
Studied dose
up to 15 mg · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
However, patients with or without diabetes showed similar decreases in visceral adiposity (as reflected by the decline in paracardiac fat) and in left ventricular mass.
2 context sentences(design, population, supporting numbers)
Summary · context
Paired cardiac magnetic resonance imaging was used to assess changes in left ventricular mass and paracardiac fat at 52 weeks.
Summary · context
In a double-blind trial, 731 patients with heart failure and a preserved ejection fraction (HFpEF) with a body mass index ≥30 kg/m² were randomly assigned in a 1:1 ratio to receive tirzepatide (up to 15 mg subcutaneously weekly) or placebo for a median of 104 weeks.
Report a problemFND-4090313114

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

Registered trials2

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

2 trials · 1 not yet recruiting · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

Not yet recruitingPhase not statedNCT07567378

CARTIZ Registry: Cartilage, Arthropathy and Imaging Under Tirzepatide in Zone-stratified Cohorts - A Four-Institute Mexican Observational Registry

JULIO GRANADOS MONTIELn = 30est. May 2026 to est. May 2029

Psoriatic Arthritis · Osteoarthitis · Knee · Diabetes (DM) · Type 2 Diabetes Mellitus (T2DM) · Obesity (Disorder) · Insulin Resistance Syndrome · Metabolic Syndrome · Heart Failure · Preserved Ejection Fraction · Coronary Artery Disease · Atrial Fibrillation (AF) · Non Alcholic Fatty Liver Disease · Sarcopenia · Pericardium

Trial page ClinicalTrials.govUpdated 12 May 2026

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.

Publication types

MeSH terms

Keywords

PepBank is a research reference. Talk to a doctor before you use any peptide.