A Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) and Obesity: The SUMMIT Trial
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)
2 other identifiers
interventional
731
10 countries
146
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 obesity
Started Apr 2021
Typical duration for phase_3 obesity
146 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 26, 2021
CompletedFirst Posted
Study publicly available on registry
April 19, 2021
CompletedStudy Start
First participant enrolled
April 20, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 2, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
July 2, 2024
CompletedResults Posted
Study results publicly available
August 20, 2025
CompletedAugust 20, 2025
August 1, 2025
3.2 years
February 26, 2021
July 2, 2025
August 15, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS)
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 .
Baseline, Week 52
First Occurrence of the Composite Endpoint of Heart Failure (HF) Outcomes
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.
Baseline Up To 160 weeks
Secondary Outcomes (9)
Change From Baseline in Exercise Capacity as Measured by 6-Minute Walk Distance (6MWD)
Baseline, Week 52
Percent Change From Baseline in Body Weight
Baseline, Week 52
Percent Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP)
Baseline, Week 52
Win Percentage of the Hierarchical Composite Endpoint
Baseline Up To 160 Weeks
Percentage of Participants With New York Heart Association (NYHA) Class Change
Week 52
- +4 more secondary outcomes
Study Arms (2)
Tirzepatide
EXPERIMENTALParticipants 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
PLACEBO COMPARATORParticipants received placebo administered SC QW.
Interventions
Eligibility Criteria
You may qualify if:
- 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)
- MWD 100-425 meters
- KCCQ CSS ≤80
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (146)
Heart Center Research
Huntsville, Alabama, 35801, United States
Westside Medical Associates of Los Angeles
Beverly Hills, California, 90211, United States
Valley Clinical Trials, Inc.
Covina, California, 91723, United States
Amicis Research Center
Granada Hills, California, 91344, United States
University of California San Diego - La Jolla
La Jolla, California, 92037, United States
Valley Clinical Trials, Inc.
Northridge, California, 91325, United States
The Lundquist Institute
Torrance, California, 90502, United States
South Denver Cardiology Associates
Littleton, Colorado, 80120, United States
Cardiology Associates of Fairfield County, P.C.
Stamford, Connecticut, 06905, United States
Excel Medical Clinical Trials
Boca Raton, Florida, 33434, United States
Clearwater Cardiovascular & Interventional Consultants M.D., P.A.
Clearwater, Florida, 33756, United States
Clearwater Cardiovascular & Interventional Consultants M.D., P.A.
Largo, Florida, 33777, United States
Infinite Clinical Research
Miami, Florida, 33133, United States
Ocala Caridovascular Research
Ocala, Florida, 34471, United States
Clearwater Cardiovascular & Interventional Consultants M.D., P.A.
Safety Harbor, Florida, 34695, United States
East Coast Institute for Research - St. Augustine
Saint Augustine, Florida, 32086, United States
Morehouse School Of Medicine
Atlanta, Georgia, 30310, United States
St. Luke's Boise Medical Center
Boise, Idaho, 83712, United States
Northwest Heart Clinical Research
Arlington Heights, Illinois, 60005, United States
Methodist Medical Center of Illinois
Peoria, Illinois, 61636, United States
Cardiovascular Research of Northwest Indiana
Munster, Indiana, 46321, United States
Midwest Heart & Vascular Specialists
Overland Park, Kansas, 66211, United States
Grace Research - Bossier
Bossier City, Louisiana, 71111, United States
The Heart Clinic - Hammond
Hammond, Louisiana, 70403, United States
Grace Research - Shreveport
Shreveport, Louisiana, 71105, United States
Maryland Cardiovascular Specialists
Baltimore, Maryland, 21229, United States
McLaren Bay Region
Bay City, Michigan, 48708, United States
St. Louis Heart and Vascular, P.C.
St Louis, Missouri, 63136, United States
Palm Research Center Tenaya
Las Vegas, Nevada, 89128, United States
The Heart House
Haddon Heights, New Jersey, 08035, United States
Lovelace Medical Center
Albuquerque, New Mexico, 87102, United States
Erie County Medical Center
Buffalo, New York, 14215, United States
Rochester General Hospital
Rochester, New York, 14621, United States
Saratoga Cardiology Associates
Saratoga Springs, New York, 12866, United States
Stony Brook University
Stony Brook, New York, 11794, United States
OnSite Clinical Solutions
Charlotte, North Carolina, 28277, United States
Aultman Hospital Research
Canton, Ohio, 44710, United States
Rama Research
Marion, Ohio, 43302, United States
Hightower Clinical Trial Services
Oklahoma City, Oklahoma, 73102, United States
Hillsboro Cardiology
Hillsboro, Oregon, 97123, United States
Capital Area Research, LLC
Camp Hill, Pennsylvania, 17011, United States
Doylestown Hospital
Doylestown, Pennsylvania, 18901, United States
UPMC Clinical Trials
Pittsburgh, Pennsylvania, 15213, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Monument Health Rapid City Hospital
Rapid City, South Dakota, 57701, United States
The Stern Cardiovascular Foundation
Germantown, Tennessee, 38138, United States
Apex Research Foundation
Jackson, Tennessee, 38301, United States
DiscoveResearch
Beaumont, Texas, 77701, United States
UT Southwestern Medical Center
Dallas, Texas, 75390, United States
North Dallas Research Associates
McKinney, Texas, 75069, United States
Sherman Clinical Research
Sherman, Texas, 75092, United States
Northwest Houston Heart Center
Tomball, Texas, 77375, United States
Intermountain Medical Center
Murray, Utah, 84107, United States
MultiCare Good Samaritan Hospital
Puyallup, Washington, 98372, United States
DIM Clínica Privada
Ramos Mejía, Buenos Aires, 1704, Argentina
Go Centro Medico San Nicolás
San Nicolás de los Arroyos, Buenos Aires, 2900, Argentina
Instituto Médico Especializado (IME)
Buenos Aires, Buenos Aires F.D., 1405, Argentina
Mautalen Salud e Investigación
Buenos Aires, Buenos Aires F.D., C1128AAF, Argentina
Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada
Buenos Aires, Buenos Aires F.D., C1425AGC, Argentina
Centro de Investigaciones Metabólicas (CINME)
Ciudad Autónoma de Buenos Aire, Buenos Air, C1027AAP, Argentina
CIPREC
Buenos Aires, Ciudad Autónoma de Buenos Aire, C1061AAS, Argentina
Instituto Médico Río Cuarto
Río Cuarto, Córdoba Province, 5800, Argentina
Instituto de Investigaciones Clinicas Rosario
Rosario, Santa Fe Province, S2000CVD, Argentina
CEMEDIC
Buenos Aires, 1407, Argentina
Fundación Respirar
Buenos Aires, 1426, Argentina
Instituto de Cardiología "Juana F. Cabral"
Corrientes, 3400, Argentina
Centro de Investigaciones Clinicas Instituto del Corazon (CICIC)
Córdoba, X5002HWE, Argentina
Hospital de Alta Complejidad "Pte. Juan Domingo Perón"
Formosa, 3600, Argentina
Centro Cardiovascular Salta
Salta, 4406, Argentina
Instituto Cardiovascular San Luis
San Luis, 5700, Argentina
Centro de Investigaciones Clinicas del Litoral
Santa Fe, 3000, Argentina
Universidade Federal de Goias
Goiânia, Goiás, 74605-020, Brazil
Hospital Angelina Caron
Campina Grande do Sul, Paraná, 83430-000, Brazil
Centro de Pesquisa Clinica do Coracao
Aracaju, Sergipe, 49055-530, Brazil
Centro de Pesquisa Sao Lucas
Campinas, São Paulo, 13034-685, Brazil
Instituto de Pesquisa clinica de Campinas
Campinas, São Paulo, 13060-080, Brazil
Loema Instituto de Pesquisa Clinica
Campinas, São Paulo, 13092133, Brazil
CAPED Centro Avancado Pesquisa e Diagnostica
Ribeirão Preto, São Paulo, 14026-900, Brazil
Pesquisare Saude
Santo André, São Paulo, 09080-110, Brazil
Fundação Faculdade Regional de Medicina de São José do Rio Preto
São José do Rio Preto, São Paulo, 15090000, Brazil
IBPClin - Instituto Brasil de Pesquisa Clínica
Rio de Janeiro, 22241-180, Brazil
CEPIC - Centro Paulista de Investigação Clínica
São Paulo, 04266-010, Brazil
Peking University First Hospital
Beijing, Beijing Municipality, 100034, China
Beijing Friendship Hospital
Beijing, Beijing Municipality, 100050, China
Lanzhou university second hospital
Lanzhou, Gansu, 730030, China
The First Hospital of Harbin Medical University
Harbin, Heilongjiang, 150001, China
Wuhan University Medical College - Hubei Zhongshan Hospital
Wuhan, Hubei, 430000, China
The Third Xiangya Hospital of Central South University
Changsha, Hunan, 410013, China
1st Hospital affiliate to Baotou medical college
Baotou, Inner Mongolia, 014010, China
Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
Nanjing, Jiangsu, 210000, China
The Second Affiliated Hospital of Nanjing Medical University
Nanjing, Jiangsu, 210011, China
The Second Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006, China
Jiangxi Pingxiang People's Hospital
Pingxiang, Jiangxi, 337055, China
Jilin Province People's Hospital
Changchun, Jilin, 130021, China
China-Japan Union Hospital
Changchun, Jilin, 130033, China
The first affiliated hospital of dalian medical university
Dalian, Liaoning, 116000, China
The People's Hospital of Liaoning Province
Shenyang, Liaoning, 110000, China
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi, 710061, China
Jinan Central Hospital
Jinan, Shandong, 250013, China
Zhongshan Hospital,Fudan University
Shanghai, Shanghai Municipality, 200032, China
Huashan Hospital Affiliated Fudan University
Shanghai, Shanghai Municipality, 200040, China
West China Hospital, Sichuan University
Chengdu, Sichuan, 610041, China
The First Affiliated Hospital of Xinjiang Medical University
Ürümqi, Xinjiang, 830054, China
CIMS Hospital - Care Institute of Medical Sciences
Ahmedabad, Gujarat, 380060, India
Medanta The Medicity
Gurugramam, Haryana, 122018, India
Narayana Institute of Cardiac Sciences
Bangalore, Karnataka, 560099, India
King Edward Memorial Hospital & Seth Gordhandas Sunderdas Medical College
Mumbai, Maharashtra, 400012, India
Government Medical College And Hospital - Nagpur
Nagpur, Maharashtra, 440009, India
Central India Cardiology and Research Institute
Nagpur, Maharashtra, 440015, India
Vijan Hospital & Research Centre
Nashik, Maharashtra, 422005, India
G.B. Pant Institute of Postgraduate Medical Education & Research
New Delhi, National Capital Territory of Delhi, 110002, India
Batra Hospital and Medical Research Centre
New Delhi, National Capital Territory of Delhi, 110062, India
AIG Hospitals
Hyderabad, Telangana, 500032, India
Meir Medical Center
Kfar Saba, Central District, 4428164, Israel
Rabin Medical Center
Petah Tikva, Central District, Israel
Sheba Medical Center
Ramat Gan, Central District, 5262100, Israel
Kaplan Medical Center
Rehovot, Central District, 7610001, Israel
Shaare Zedek Medical Center
Jerusalem, Jerusalem, 9013102, Israel
Hadassah Medical Center
Jerusalem, Jerusalem, 9112001, Israel
Hillel Yaffe Medical Center
Hadera, Northern District, 3810101, Israel
Rambam Health Care Campus
Haifa, Northern District, 3109601, Israel
Galilee Medical Center
Nahariya, Northern District, 2210001, Israel
Barzilai Medical Center
Ashkelon, Southern District, 7830604, Israel
Sourasky Medical Center
Tel Aviv, Tell Abīb, 6423906, Israel
CIMAB SA de CV
Torreón, Coahuila, 27000, Mexico
Virgen Cardiovascular Research SC
Guadalajara, Jalisco, 44670, Mexico
Cardiolink Clin Trials
Monterrey, Nuevo León, 64060, Mexico
Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
Monterrey, Nuevo León, 66460, Mexico
Fundación Cardiovascular de Aguascalientes A.C.
Aguascalientes, 20230, Mexico
Hospital Cardiologica Aguescalientes
Aguascalientes, 20230, Mexico
Centro de Estudios Clínicos de Querétaro (CECLIQ)
Querétaro, 76000, Mexico
Clinical Research Center - Universidad Central del Caribe (CRC - UCC)
Bayamón, 00956, Puerto Rico
Research and Cardiovascular Corp.
Ponce, 00717, Puerto Rico
Ivanovo Regional Healthcare Institution Cardiology Dispensary
Ivanovo, Ivanovo Oblast, 153012, Russia
Russian Cardiology Research and Production Complex
Moscow, Moscow, 121552, Russia
Russian Medical Academy of Postgraduate Education
Moscow, Moscow, 125993, Russia
Ryazan Regional Clinical Cardiological Dispensary
Ryazan, Ryazan Oblast, 390026, Russia
Astarta Clinic
Saint Petersburg, Sankt-Peterburg, 199226, Russia
Izhevsk City Clinical Hospital Number 9
Izhevsk, Udmurtiya Republic, 426063, Russia
Chung Shan Medical University Hospital
Taichung, Taichung, 402, Taiwan
Mackay Memorial Hospital-Hsinchu
Hsinchu, 300, Taiwan
Kaohsiung Medical University Hospital
Kaohsiung City, Taiwan
National Taiwan University Hospital
Taipei, 10002, Taiwan
Taipei Medical University Hospital
Taipei, 110, Taiwan
Taipei Veterans General Hospital
Taipei, 11217, Taiwan
Chang Gung Medical Foundation-Linkou Branch
Taoyuan District, 333, Taiwan
Related Publications (7)
Packer M, Zile MR, Kramer CM, DiMaria JM, Baum SJ, Litwin SE, Murakami M, Zhou C, Ou Y, Koeneman L, Borlaug BA; SUMMIT Trial Study Group. 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. J Am Coll Cardiol. 2025 Sep 9;86(10):696-707. doi: 10.1016/j.jacc.2025.06.058.
PMID: 40903131DERIVEDBorlaug BA, Zile MR, Kramer CM, Ye W, Ou Y, Hurt K, Murakami M, Packer M; SUMMIT Trial Study Group. Impact of Body Mass Index, Central Adiposity, and Weight Loss on the Benefits of Tirzepatide in HFpEF: The SUMMIT Trial. J Am Coll Cardiol. 2025 Jul 29;86(4):242-255. doi: 10.1016/j.jacc.2025.04.059.
PMID: 40701669DERIVEDPacker M, Zile MR, Kramer CM, Murakami M, Ou Y, Borlaug BA; SUMMIT Trial Study Group. Interplay of Chronic Kidney Disease and the Effects of Tirzepatide in Patients With Heart Failure, Preserved Ejection Fraction, and Obesity: The SUMMIT Trial. J Am Coll Cardiol. 2025 May 13;85(18):1721-1735. doi: 10.1016/j.jacc.2025.03.009. Epub 2025 Mar 31.
PMID: 40162940DERIVEDKramer CM, Borlaug BA, Zile MR, Ruff D, DiMaria JM, Menon V, Ou Y, Zarante AM, Hurt KC, Murakami M, Packer M; SUMMIT Trial Study Group. Tirzepatide Reduces LV Mass and Paracardiac Adipose Tissue in Obesity-Related Heart Failure: SUMMIT CMR Substudy. J Am Coll Cardiol. 2025 Feb 25;85(7):699-706. doi: 10.1016/j.jacc.2024.11.001. Epub 2024 Nov 18.
PMID: 39566869DERIVEDZile MR, Borlaug BA, Kramer CM, Baum SJ, Litwin SE, Menon V, Ou Y, Weerakkody GJ, Hurt KC, Kanu C, Murakami M, Packer M; SUMMIT Trial Study Group. Effects of Tirzepatide on the Clinical Trajectory of Patients With Heart Failure, Preserved Ejection Fraction, and Obesity. Circulation. 2025 Mar 11;151(10):656-668. doi: 10.1161/CIRCULATIONAHA.124.072679. Epub 2024 Nov 18.
PMID: 39556714DERIVEDPacker M, Zile MR, Kramer CM, Baum SJ, Litwin SE, Menon V, Ge J, Weerakkody GJ, Ou Y, Bunck MC, Hurt KC, Murakami M, Borlaug BA; SUMMIT Trial Study Group. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2025 Jan 30;392(5):427-437. doi: 10.1056/NEJMoa2410027. Epub 2024 Nov 16.
PMID: 39555826DERIVEDBorlaug BA, Zile MR, Kramer CM, Baum SJ, Hurt K, Litwin SE, Murakami M, Ou Y, Upadhyay N, Packer M. 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. Nat Med. 2025 Feb;31(2):544-551. doi: 10.1038/s41591-024-03374-z. Epub 2024 Nov 17.
PMID: 39551891DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Eli Lilly and Company
Study Officials
- STUDY DIRECTOR
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 26, 2021
First Posted
April 19, 2021
Study Start
April 20, 2021
Primary Completion
July 2, 2024
Study Completion
July 2, 2024
Last Updated
August 20, 2025
Results First Posted
August 20, 2025
Record last verified: 2025-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Data are available 6 months after the primary publication and approval of the indication studied in the US and European (EU), whichever is later. Data will be indefinitely available for requesting.
- Access Criteria
- A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.