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NCT04847557

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

Completed Phase 3 Results posted Last updated 20 August 2025
What this trial tests

Phase 3 trial testing Tirzepatide in Obesity in 731 participants. Completed in 2 July 2024.

Timeline
20 April 2021
Primary endpoint
2 July 2024
2 July 2024

Quick facts

Lead sponsorEli Lilly and Company
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment731
Start date20 April 2021
Primary completion2 July 2024
Estimated completion2 July 2024
Sites146 locations across Russia, Taiwan, Israel, Mexico, Argentina, Puerto Rico, China, United States

Drugs / interventions tested

Conditions studied

Sponsor

Eli Lilly and Company — full company profile →

Who can join

40 and older, any sex, with Obesity or Heart Failure With Preserved Ejection Fraction (HFpEF). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) Primary · Baseline, Week 52

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

GroupValue95% CI
Tirzepatide - MTD19.51± 1.24
Placebo12.68± 1.25
First Occurrence of the Composite Endpoint of Heart Failure (HF) Outcomes Primary · Baseline Up To 160 weeks

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 o

GroupValue95% CI
Tirzepatide - MTD36
Placebo56
Change From Baseline in Exercise Capacity as Measured by 6-Minute Walk Distance (6MWD) Secondary · Baseline, Week 52

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.

GroupValue95% CI
Tirzepatide - MTD26.04± 3.81
Placebo10.10± 3.94
Percent Change From Baseline in Body Weight Secondary · Baseline, Week 52

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.

GroupValue95% CI
Tirzepatide - MTD-13.85± 0.43
Placebo-2.24± 0.46
Percent Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) Secondary · Baseline, Week 52

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.

GroupValue95% CI
Tirzepatide - MTD-38.76± 4.47
Placebo-5.88± 5.25
Win Percentage of the Hierarchical Composite Endpoint Secondary · Baseline Up To 160 Weeks

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

GroupValue95% CI
Tirzepatide - MTD57.90
Placebo35.43
Percentage of Participants With New York Heart Association (NYHA) Class Change Secondary · Week 52

Percentage of participants with NYHA class change at Week 52 was reported.

GroupValue95% CI
Tirzepatide - MTD33.27
Placebo20.39
Number of Participants With Time to All-Cause Death Secondary · Baseline Up To 160 Weeks

All-cause mortality is death due to any cause. Number of participants with time to all-cause mortality are presented.

GroupValue95% CI
Tirzepatide - MTD19
Placebo15
Number of Participants With Time to First Occurrence of HF Events Secondary · Baseline Up To 160 Weeks

Number of participants with time to first occurrence of HF events are reported.

GroupValue95% CI
Tirzepatide - MTD29
Placebo52
Number of HF Events and All-Cause Death Secondary · Baseline Up To 160 Weeks.

Number of HF events and all-cause death are reported.

GroupValue95% CI
Tirzepatide - MTD61
Placebo82
Number of Recurrent HF Events Secondary · Baseline Up To 160 Weeks.

Number of recurrent HF events were reported.

GroupValue95% CI
Tirzepatide - MTD44
Placebo68

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline Up To 162 Weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Tirzepatide - MTD
Serious: 96/364 (26%)
Deaths: 19/364
Placebo
Serious: 94/367 (26%)
Deaths: 15/367

Serious adverse events (186 terms)

ReactionSystemTirzepatide - MTDPlacebo
Cardiac failureCardiac disorders
Cardiac failure congestiveCardiac disorders
Atrial fibrillationCardiac disorders
Acute myocardial infarctionCardiac disorders
Cholecystitis acuteHepatobiliary disorders
CellulitisInfections and infestations
PneumoniaInfections and infestations
AnaemiaBlood and lymphatic system disorders
Angina unstableCardiac disorders
Urinary tract infectionInfections and infestations
Acute kidney injuryRenal and urinary disorders
Septic shockInfections and infestations
Chronic kidney diseaseRenal and urinary disorders
Acute coronary syndromeCardiac disorders
Cardio-respiratory arrestCardiac disorders
Coronary artery diseaseCardiac disorders
Sinus node dysfunctionCardiac disorders
DiarrhoeaGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
Obstructive pancreatitisGastrointestinal disorders
Upper gastrointestinal haemorrhageGastrointestinal disorders
Sudden deathGeneral disorders
Abdominal abscessInfections and infestations
AppendicitisInfections and infestations
Covid-19Infections and infestations
Other adverse events (12 terms — click to expand)

ReactionSystemTirzepatide - MTDPlacebo
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
ConstipationGastrointestinal disorders
Covid-19Infections and infestations
VomitingGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
DizzinessNervous system disorders
Urinary tract infectionInfections and infestations
DyspepsiaGastrointestinal disorders
HypotensionVascular disorders
Cardiac failureCardiac disorders
Abdominal pain upperGastrointestinal disorders

Most-reported serious reactions: Cardiac failure, Cardiac failure congestive, Atrial fibrillation, Acute myocardial infarction, Cholecystitis acute, Cellulitis, Pneumonia, Anaemia.

Data from ClinicalTrials.gov NCT04847557 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity.
    Packer M, Zile MR, Kramer CM, Baum SJ, et al · · 2025 · cited 475× · PMID 39555826 · DOI 10.1056/nejmoa2410027
  2. Obesity and heart failure with preserved ejection fraction: new insights and pathophysiological targets.
    Borlaug BA, Jensen MD, Kitzman DW, Lam CSP, et al · · 2023 · cited 280× · PMID 35880317 · DOI 10.1093/cvr/cvac120
  3. Dapagliflozin for heart failure according to body mass index: the DELIVER trial.
    Adamson C, Kondo T, Jhund PS, de Boer RA, et al · · 2022 · cited 128× · PMID 36029309 · DOI 10.1093/eurheartj/ehac481
  4. Heart Failure with Preserved Ejection Fraction: Mechanisms and Treatment Strategies.
    Omote K, Verbrugge FH, Borlaug BA. · · 2022 · cited 126× · PMID 34379445 · DOI 10.1146/annurev-med-042220-022745
  5. Heart Failure With Preserved Ejection Fraction: Heterogeneous Syndrome, Diverse Preclinical Models.
    Roh J, Hill JA, Singh A, Valero-Muñoz M, et al · · 2022 · cited 124× · PMID 35679364 · DOI 10.1161/circresaha.122.320257
  6. Tirzepatide Reduces LV Mass and Paracardiac Adipose Tissue in Obesity-Related Heart Failure: SUMMIT CMR Substudy.
    Kramer CM, Borlaug BA, Zile MR, Ruff D, et al · · 2025 · cited 93× · PMID 39566869 · DOI 10.1016/j.jacc.2024.11.001
  7. Long-Term Changes in Cardiac Structure and Function Following Bariatric Surgery.
    Sorimachi H, Obokata M, Omote K, Reddy YNV, et al · · 2022 · cited 86× · PMID 36229085 · DOI 10.1016/j.jacc.2022.08.738
  8. Transforming obesity: The advancement of multi-receptor drugs.
    Kusminski CM, Perez-Tilve D, Müller TD, DiMarchi RD, et al · · 2024 · cited 77× · PMID 39059360 · DOI 10.1016/j.cell.2024.06.003

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Other trials of Tirzepatide

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