Primary outcomeLeast squares mean· Baseline, Week 52
Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS)
| Group | Value (Score on a scale) | Spread |
|---|---|---|
| Tirzepatide - MTD | 19.51 | 1.24 |
| Placebo | 12.68 | 1.25 |
Trial · Interventional
CompletedPhase 3Results postedRegistry dataA Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) and Obesity: The SUMMIT Trial
Overview
- Status
- Completed
- Phase
- Phase 3
- Enrollment
- 731 participants (actual)
- Sponsor
- Eli Lilly and Company · Industry
- Design
- Randomized · Double masking
- Countries
10 countries
United States, Argentina, Brazil, China, India, Israel, Mexico, Puerto Rico, Russia, Taiwan
- Start
- 20 Apr 2021
- Primary completion
- 2 Jul 2024
- Completion
- 2 Jul 2024
- First posted
- 19 Apr 2021
- Last update posted
- 20 Aug 2025
- Conditions
- Obesity · Heart Failure With Preserved Ejection Fraction (HFpEF)
Timeline
1 trial · 1 completed · 1 with posted results
- Completed
- Ongoing
- Not yet recruiting
- Stopped
- Estimated dates (est.)
- Results posted
20212022202320242025
- Ph 3
A Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) and Obesity: The SUMMIT Trial
NCT0484755720 Apr 2021 to 2 Jul 2024
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
The main purpose of this study is to assess the efficacy and safety of Tirzepatide (LY3298176) in participants with heart failure with preserved ejection fraction and obesity.
Interventions
- TirzepatideDrug
- PlaceboOther
Arms2
Experimental
Tirzepatide
Participants received a starting dose of 2.5 milligrams (mg) tirzepatide administered subcutaneously (SC) once weekly (QW) and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or maximum tolerated dose (MTD) tolerated by the participant (5 mg QW or 10 mg QW).
Placebo comparator
Placebo
Participants received placebo administered SC QW.
Primary outcomes2
Outcomes the sponsor listed as primary.
Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS)
Time frame · Baseline, Week 52
Registry description
The KCCQ is a 23-item, participant self-administered questionnaire that assesses impacts of heart failure "over the past 2 weeks" on the following 7 domains: * Physical Limitation (6) * Symptom Stability (1) * Symptom Frequency (4) * Symptom Burden (3) * Self-Efficacy (2) * Quality of Life (3) * Social Limitation (4) Each of the 23 individual items are answered on Likert scales of varying lengths (5, 6, or 7-point scales). KCCQ-CSS includes the symptom and physical limitation domains of the KCCQ. Scores are obtained by averaging the associated individual items and transforming the score to a 0 to 100 range. Higher scores indicate better health status. Least Square (LS) mean was determined using ANCOVA model with Baseline + HF Decompensation Within 12 Months of Screening + T2DM Status + Baseline BMI group (\<35, \>=35 kg/m2) + Treatment (Type III sum of squares) as variables .
First Occurrence of the Composite Endpoint of Heart Failure (HF) Outcomes
Time frame · Baseline Up To 160 weeks
Registry description
Clinical Endpoint Committe confirmed Occurrences of CV outcomes were reported here. HF outcomes consisted of cardiovascular death and HF events. The HF events were defined as worsening clinical symptoms or signs related to HF, which are meaningful to the participant and require intensification of treatment characterized by 1 or more of the following: * hospitalization for heart failure regardless of duration or treatment received * use of intravenous drug, usually an intravenous diuretic, but may include intravenous vasodilators or positive inotropic drugs, or * augmentation or increase in oral diuretic therapy.
Secondary outcomes(9)
Change From Baseline in Exercise Capacity as Measured by 6-Minute Walk Distance (6MWD)
Time frame · Baseline, Week 52
Registry description
Participants performed an exercise capacity assessment using the 6-Minute Walk Test (6MWT) and the distance covered (6MWD) was assessed in meters. The 6MWT was performed indoors on a straight, flat, hard surface that is at least 30 meters in length. The greater distance walked meant better physical capacity. LS Mean was determined using ANCOVA model with Baseline + HF Decompensation Within 12 Months of Screening + T2DM Status + Baseline BMI group (\<35, \>=35 kg/m2) + Treatment (Type III sum of squares) as variables.
Percent Change From Baseline in Body Weight
Time frame · Baseline, Week 52
Registry description
Percent change in bodyweight was reported. LS mean was determined using ANCOVA model with Baseline + HF Decompensation Within 12 Months of Screening + T2DM Status + Baseline BMI group (\<35, \>=35 kg/m2) + Treatment (Type III sum of squares) as variables.
Percent Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP)
Time frame · Baseline, Week 52
Registry description
Percent change from baseline in hsCRP was reported. LS Mean was determined using ANCOVA model with log (actual measurement/baseline) = log (baseline) + HF decompensation within 12 months of screening + T2DM status + baseline BMI group (\<35, \>=35 kg/m2) + Treatment (Type III sum of squares) as variables.
Win Percentage of the Hierarchical Composite Endpoint
Time frame · Baseline Up To 160 Weeks
Registry description
Hierarchical Composite Endpoint included time to all-cause death, number of HF events, time to first HF events, KCCQ-CSS, 6MWD. The winner was determined in each pair-wise comparison in the following order: * A delayed first occurrence of all-cause death * If the pair cannot be differentiated based on death, winner has fewer HF events * If the pair cannot be differentiated by number of HF events, winner has delayed time to occurrence of first HF event * If the pair still cannot be differentiated, winner has a more favorable category for change from baseline in 6MWD * If the pair still cannot be differentiated, winner has a more favorable category for change from baseline in KCCQ-CSS * Otherwise the pair will be recorded as tied. Reported unit is the total percent of "wins" for each treatment group from performing such a hierarchical comparison across stratification factors in the study.
Percentage of Participants With New York Heart Association (NYHA) Class Change
Time frame · Week 52
Registry description
Percentage of participants with NYHA class change at Week 52 was reported.
Number of Participants With Time to All-Cause Death
Time frame · Baseline Up To 160 Weeks
Registry description
All-cause mortality is death due to any cause. Number of participants with time to all-cause mortality are presented.
Number of Participants With Time to First Occurrence of HF Events
Time frame · Baseline Up To 160 Weeks
Registry description
Number of participants with time to first occurrence of HF events are reported.
Number of HF Events and All-Cause Death
Time frame · Baseline Up To 160 Weeks.
Registry description
Number of HF events and all-cause death are reported.
Number of Recurrent HF Events
Time frame · Baseline Up To 160 Weeks.
Registry description
Number of recurrent HF events were reported.
Posted results
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
Primary outcome results
Primary outcomeNumber· Baseline Up To 160 weeks
First Occurrence of the Composite Endpoint of Heart Failure (HF) Outcomes
| Group | Value (Number of events) |
|---|---|
| Tirzepatide - MTD | 36 |
| Placebo | 56 |
Secondary and other outcome results(6)
Secondary outcomeLeast squares mean· Baseline, Week 52
Change From Baseline in Exercise Capacity as Measured by 6-Minute Walk Distance (6MWD)
| Group | Value (meters) | Spread |
|---|---|---|
| Tirzepatide - MTD | 26.04 | 3.81 |
| Placebo | 10.10 | 3.94 |
Secondary outcomeLeast squares mean· Baseline, Week 52
Percent Change From Baseline in Body Weight
| Group | Value (Percent change) | Spread |
|---|---|---|
| Tirzepatide - MTD | -13.85 | 0.43 |
| Placebo | -2.24 | 0.46 |
Secondary outcomeLeast squares mean· Baseline, Week 52
Percent Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP)
| Group | Value (Percent change) | Spread |
|---|---|---|
| Tirzepatide - MTD | -38.76 | 4.47 |
| Placebo | -5.88 | 5.25 |
Secondary outcomeNumber· Baseline Up To 160 Weeks
Win Percentage of the Hierarchical Composite Endpoint
| Group | Value (Win percentage) |
|---|---|
| Tirzepatide - MTD | 57.90 |
| Placebo | 35.43 |
Secondary outcomeNumber· Week 52
Percentage of Participants With New York Heart Association (NYHA) Class Change
| Group | Value (Percentage of participants) |
|---|---|
| Tirzepatide - MTD | 33.27 |
| Placebo | 20.39 |
Secondary outcomeCount of participants· Baseline Up To 160 Weeks
Number of Participants With Time to All-Cause Death
| Group | Value (Participants) |
|---|---|
| Tirzepatide - MTD | 19 |
| Placebo | 15 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Tirzepatide - MTDParticipants received a starting dose of 2.5 mg tirzepatide administered SC QW and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or MTD tolerated by the participant (5 mg QW or 10 mg QW). | 19 / 364 | 96 / 364 | 221 / 364 |
| PlaceboParticipants received placebo administered SC QW. | 15 / 367 | 94 / 367 | 137 / 367 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies8
Studies that cite this trial.
Studies with results
7 studies on this page
Indexing hint: Randomized controlled trial · 2025
10 results
Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial.
Borlaug et al. 2025Nature medicinecited by 117
PMID 39551891PMC11835708DOI 10.1038/s41591-024-03374-zPUB-39551891
CC BY10 results
Indexing hint: Randomized controlled trial · 2025
5 results
Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity.
Packer et al. 2025The New England journal of medicinecited by 758
PMID 39555826DOI 10.1056/nejmoa2410027PUB-39555826
Full text at the publisher5 results
Indexing hint: Randomized controlled trial · 2025
8 results
Effects of Tirzepatide on the Clinical Trajectory of Patients With Heart Failure, Preserved Ejection Fraction, and Obesity.
Zile et al. 2025Circulationcited by 58
PMID 39556714PMC11893002DOI 10.1161/circulationaha.124.072679PUB-39556714
Free to read · publisher termsCC BY-NC-ND8 results
Indexing hint: Randomized controlled trial · 2025
5 results
Tirzepatide Reduces LV Mass and Paracardiac Adipose Tissue in Obesity-Related Heart Failure: SUMMIT CMR Substudy.
Kramer et al. 2025Journal of the American College of Cardiologycited by 124
PMID 39566869DOI 10.1016/j.jacc.2024.11.001PUB-39566869
Full text at the publisher5 results
Indexing hint: Randomized controlled trial · 2025
8 results
Interplay of Chronic Kidney Disease and the Effects of Tirzepatide in Patients With Heart Failure, Preserved Ejection Fraction, and Obesity: The SUMMIT Trial.
Packer et al. 2025Journal of the American College of Cardiologycited by 27
PMID 40162940DOI 10.1016/j.jacc.2025.03.009PUB-40162940
Full text at the publisher8 results
Indexing hint: Randomized controlled trial · 2025
11 results
Impact of Body Mass Index, Central Adiposity, and Weight Loss on the Benefits of Tirzepatide in HFpEF: The SUMMIT Trial.
Borlaug et al. 2025Journal of the American College of Cardiologycited by 27
PMID 40701669DOI 10.1016/j.jacc.2025.04.059PUB-40701669
Full text at the publisher11 results
Indexing hint: Randomized controlled trial · 2025
14 results
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 et al. 2025Journal of the American College of Cardiologycited by 11
PMID 40903131DOI 10.1016/j.jacc.2025.06.058PUB-40903131
Full text at the publisher14 results
More studies
1 study on this page
PubMed tag: none · 2026
Effects of Tirzepatide in Obesity-Related HFpEF by Sex: A Prespecified Secondary Analysis From the SUMMIT Trial.
Borlaug et al. 2026JACC. Heart failure
PMID 42417681PMC13398731DOI 10.1016/j.jchf.2026.103218PUB-42417681
Rights unknown
Other registry references
References listed at the registry that are not in PepBank. They link to PubMed.
- DerivedReese-Petersen AL, Holm Nielsen S, Bulow Sand JM, Schattenberg JM, Bugianesi E, Karsdal MA. The sclerotic component of metabolic syndrome: Fibroblast activities may be the central common denominator driving organ function loss and death. Diabetes Obes Metab. 2024 Jul;26(7):2554-2566. doi: 10.1111/dom.15615. Epub 2024 May 3. PMID 38699780
Eligibility
Who could join, as posted.
- Sex
- All
- Age
- from 40 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria:
* Have a diagnosis of stable heart failure (NYHA class II-IV) and left ventricular ejection fraction (LVEF) ≥50%
* Elevated NT-proBNP (N-terminal pro B-type natriuretic peptide) \> 200 picogram/milliliter (pg/ml) for participants without atrial fibrillation (AF), or \>600 pg/ml for participants with AF, Structural heart disease (Left atrial enlargement) or Elevated left ventricular filling pressure
* Estimated glomerular filtration rate (eGFR) \<70 milliliter (ml)/minute (min)/1.73m² at screening, or HF decompensation within 12 months of screening,
* Stable dose of heart failure medications within 4 weeks of screening
* Body mass index (BMI) ≥30 kilograms per meter squared (kg/m²)
* 6MWD 100-425 meters
* KCCQ CSS ≤80
Exclusion Criteria:
* Have had a major cardiovascular event within the last 90 days of screening
* Have had acute decompensated heart failure within 4 weeks of screening
* Have non cardiac causes of functional impairment such as pulmonary arterial hypertension (PAH), severe chronic obstructive pulmonary disease (COPD), anemia, thyroid disease, musculoskeletal disease or orthopedic conditions
* Presence of cardiac amyloidosis, cardiac accumulation disease, cardiomyopathy and severe valvular heart disease
* HbA1c ≥9.5% or uncontrolled diabetes
* History of proliferative diabetic retinopathy or diabetic maculopathy
* Have a history of pancreatitis
* eGFR \<15 mL/min/1.73 m² or requiring dialysis at screening
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