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

NCT ID: NCT04847557

Last Updated: 2025-08-20

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

731 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-20

Study Completion Date

2024-07-02

Brief Summary

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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.

Detailed Description

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The study will continue until approximately 52 weeks after the last participant is randomized. The maximum duration of an individual's participation is estimated to be \~120 weeks and will depend on duration of study enrollment.

Conditions

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Obesity Heart Failure With Preserved Ejection Fraction (HFpEF)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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).

Group Type EXPERIMENTAL

Tirzepatide

Intervention Type DRUG

Administered SC

Placebo

Participants received placebo administered SC QW.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Administered SC

Interventions

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Tirzepatide

Administered SC

Intervention Type DRUG

Placebo

Administered SC

Intervention Type OTHER

Other Intervention Names

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LY3298176

Eligibility Criteria

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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
Minimum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eli Lilly and Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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Heart Center Research

Huntsville, Alabama, United States

Site Status

Westside Medical Associates of Los Angeles

Beverly Hills, California, United States

Site Status

Valley Clinical Trials, Inc.

Covina, California, United States

Site Status

Amicis Research Center

Granada Hills, California, United States

Site Status

University of California San Diego - La Jolla

La Jolla, California, United States

Site Status

Valley Clinical Trials, Inc.

Northridge, California, United States

Site Status

The Lundquist Institute

Torrance, California, United States

Site Status

South Denver Cardiology Associates

Littleton, Colorado, United States

Site Status

Cardiology Associates of Fairfield County, P.C.

Stamford, Connecticut, United States

Site Status

Excel Medical Clinical Trials

Boca Raton, Florida, United States

Site Status

Clearwater Cardiovascular & Interventional Consultants M.D., P.A.

Clearwater, Florida, United States

Site Status

Clearwater Cardiovascular & Interventional Consultants M.D., P.A.

Largo, Florida, United States

Site Status

Infinite Clinical Research

Miami, Florida, United States

Site Status

Ocala Caridovascular Research

Ocala, Florida, United States

Site Status

Clearwater Cardiovascular & Interventional Consultants M.D., P.A.

Safety Harbor, Florida, United States

Site Status

East Coast Institute for Research - St. Augustine

Saint Augustine, Florida, United States

Site Status

Morehouse School Of Medicine

Atlanta, Georgia, United States

Site Status

St. Luke's Boise Medical Center

Boise, Idaho, United States

Site Status

Northwest Heart Clinical Research

Arlington Heights, Illinois, United States

Site Status

Methodist Medical Center of Illinois

Peoria, Illinois, United States

Site Status

Cardiovascular Research of Northwest Indiana

Munster, Indiana, United States

Site Status

Midwest Heart & Vascular Specialists

Overland Park, Kansas, United States

Site Status

Grace Research - Bossier

Bossier City, Louisiana, United States

Site Status

The Heart Clinic - Hammond

Hammond, Louisiana, United States

Site Status

Grace Research - Shreveport

Shreveport, Louisiana, United States

Site Status

Maryland Cardiovascular Specialists

Baltimore, Maryland, United States

Site Status

McLaren Bay Region

Bay City, Michigan, United States

Site Status

St. Louis Heart and Vascular, P.C.

St Louis, Missouri, United States

Site Status

Palm Research Center Tenaya

Las Vegas, Nevada, United States

Site Status

The Heart House

Haddon Heights, New Jersey, United States

Site Status

Lovelace Medical Center

Albuquerque, New Mexico, United States

Site Status

Erie County Medical Center

Buffalo, New York, United States

Site Status

Rochester General Hospital

Rochester, New York, United States

Site Status

Saratoga Cardiology Associates

Saratoga Springs, New York, United States

Site Status

Stony Brook University

Stony Brook, New York, United States

Site Status

OnSite Clinical Solutions

Charlotte, North Carolina, United States

Site Status

Aultman Hospital Research

Canton, Ohio, United States

Site Status

Rama Research

Marion, Ohio, United States

Site Status

Hightower Clinical Trial Services

Oklahoma City, Oklahoma, United States

Site Status

Hillsboro Cardiology

Hillsboro, Oregon, United States

Site Status

Capital Area Research, LLC

Camp Hill, Pennsylvania, United States

Site Status

Doylestown Hospital

Doylestown, Pennsylvania, United States

Site Status

UPMC Clinical Trials

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Monument Health Rapid City Hospital

Rapid City, South Dakota, United States

Site Status

The Stern Cardiovascular Foundation

Germantown, Tennessee, United States

Site Status

Apex Research Foundation

Jackson, Tennessee, United States

Site Status

DiscoveResearch

Beaumont, Texas, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

North Dallas Research Associates

McKinney, Texas, United States

Site Status

Sherman Clinical Research

Sherman, Texas, United States

Site Status

Northwest Houston Heart Center

Tomball, Texas, United States

Site Status

Intermountain Medical Center

Murray, Utah, United States

Site Status

MultiCare Good Samaritan Hospital

Puyallup, Washington, United States

Site Status

DIM Clínica Privada

Ramos Mejía, Buenos Aires, Argentina

Site Status

Go Centro Medico San Nicolás

San Nicolás de los Arroyos, Buenos Aires, Argentina

Site Status

Instituto Médico Especializado (IME)

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

Mautalen Salud e Investigación

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

Centro de Investigaciones Metabólicas (CINME)

Ciudad Autónoma de Buenos Aire, Buenos Air, Argentina

Site Status

CIPREC

Buenos Aires, Ciudad Autónoma de Buenos Aire, Argentina

Site Status

Instituto Médico Río Cuarto

Río Cuarto, Córdoba Province, Argentina

Site Status

Instituto de Investigaciones Clinicas Rosario

Rosario, Santa Fe Province, Argentina

Site Status

CEMEDIC

Buenos Aires, , Argentina

Site Status

Fundación Respirar

Buenos Aires, , Argentina

Site Status

Instituto de Cardiología "Juana F. Cabral"

Corrientes, , Argentina

Site Status

Centro de Investigaciones Clinicas Instituto del Corazon (CICIC)

Córdoba, , Argentina

Site Status

Hospital de Alta Complejidad "Pte. Juan Domingo Perón"

Formosa, , Argentina

Site Status

Centro Cardiovascular Salta

Salta, , Argentina

Site Status

Instituto Cardiovascular San Luis

San Luis, , Argentina

Site Status

Centro de Investigaciones Clinicas del Litoral

Santa Fe, , Argentina

Site Status

Universidade Federal de Goias

Goiânia, Goiás, Brazil

Site Status

Hospital Angelina Caron

Campina Grande do Sul, Paraná, Brazil

Site Status

Centro de Pesquisa Clinica do Coracao

Aracaju, Sergipe, Brazil

Site Status

Centro de Pesquisa Sao Lucas

Campinas, São Paulo, Brazil

Site Status

Instituto de Pesquisa clinica de Campinas

Campinas, São Paulo, Brazil

Site Status

Loema Instituto de Pesquisa Clinica

Campinas, São Paulo, Brazil

Site Status

CAPED Centro Avancado Pesquisa e Diagnostica

Ribeirão Preto, São Paulo, Brazil

Site Status

Pesquisare Saude

Santo André, São Paulo, Brazil

Site Status

Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José do Rio Preto, São Paulo, Brazil

Site Status

IBPClin - Instituto Brasil de Pesquisa Clínica

Rio de Janeiro, , Brazil

Site Status

CEPIC - Centro Paulista de Investigação Clínica

São Paulo, , Brazil

Site Status

Peking University First Hospital

Beijing, Beijing Municipality, China

Site Status

Beijing Friendship Hospital

Beijing, Beijing Municipality, China

Site Status

Lanzhou university second hospital

Lanzhou, Gansu, China

Site Status

The First Hospital of Harbin Medical University

Harbin, Heilongjiang, China

Site Status

Wuhan University Medical College - Hubei Zhongshan Hospital

Wuhan, Hubei, China

Site Status

The Third Xiangya Hospital of Central South University

Changsha, Hunan, China

Site Status

1st Hospital affiliate to Baotou medical college

Baotou, Inner Mongolia, China

Site Status

Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School

Nanjing, Jiangsu, China

Site Status

The Second Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, China

Site Status

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status

Jiangxi Pingxiang People's Hospital

Pingxiang, Jiangxi, China

Site Status

Jilin Province People's Hospital

Changchun, Jilin, China

Site Status

China-Japan Union Hospital

Changchun, Jilin, China

Site Status

The first affiliated hospital of dalian medical university

Dalian, Liaoning, China

Site Status

The People's Hospital of Liaoning Province

Shenyang, Liaoning, China

Site Status

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, China

Site Status

Jinan Central Hospital

Jinan, Shandong, China

Site Status

Zhongshan Hospital,Fudan University

Shanghai, Shanghai Municipality, China

Site Status

Huashan Hospital Affiliated Fudan University

Shanghai, Shanghai Municipality, China

Site Status

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Site Status

The First Affiliated Hospital of Xinjiang Medical University

Ürümqi, Xinjiang, China

Site Status

CIMS Hospital - Care Institute of Medical Sciences

Ahmedabad, Gujarat, India

Site Status

Medanta The Medicity

Gurugramam, Haryana, India

Site Status

Narayana Institute of Cardiac Sciences

Bangalore, Karnataka, India

Site Status

King Edward Memorial Hospital & Seth Gordhandas Sunderdas Medical College

Mumbai, Maharashtra, India

Site Status

Government Medical College And Hospital - Nagpur

Nagpur, Maharashtra, India

Site Status

Central India Cardiology and Research Institute

Nagpur, Maharashtra, India

Site Status

Vijan Hospital & Research Centre

Nashik, Maharashtra, India

Site Status

G.B. Pant Institute of Postgraduate Medical Education & Research

New Delhi, National Capital Territory of Delhi, India

Site Status

Batra Hospital and Medical Research Centre

New Delhi, National Capital Territory of Delhi, India

Site Status

AIG Hospitals

Hyderabad, Telangana, India

Site Status

Meir Medical Center

Kfar Saba, Central District, Israel

Site Status

Rabin Medical Center

Petah Tikva, Central District, Israel

Site Status

Sheba Medical Center

Ramat Gan, Central District, Israel

Site Status

Kaplan Medical Center

Rehovot, Central District, Israel

Site Status

Shaare Zedek Medical Center

Jerusalem, Jerusalem, Israel

Site Status

Hadassah Medical Center

Jerusalem, Jerusalem, Israel

Site Status

Hillel Yaffe Medical Center

Hadera, Northern District, Israel

Site Status

Rambam Health Care Campus

Haifa, Northern District, Israel

Site Status

Galilee Medical Center

Nahariya, Northern District, Israel

Site Status

Barzilai Medical Center

Ashkelon, Southern District, Israel

Site Status

Sourasky Medical Center

Tel Aviv, Tell Abīb, Israel

Site Status

CIMAB SA de CV

Torreón, Coahuila, Mexico

Site Status

Virgen Cardiovascular Research SC

Guadalajara, Jalisco, Mexico

Site Status

Cardiolink Clin Trials

Monterrey, Nuevo León, Mexico

Site Status

Hospital Universitario "Dr. Jose Eleuterio Gonzalez"

Monterrey, Nuevo León, Mexico

Site Status

Fundación Cardiovascular de Aguascalientes A.C.

Aguascalientes, , Mexico

Site Status

Hospital Cardiologica Aguescalientes

Aguascalientes, , Mexico

Site Status

Centro de Estudios Clínicos de Querétaro (CECLIQ)

Querétaro, , Mexico

Site Status

Clinical Research Center - Universidad Central del Caribe (CRC - UCC)

Bayamón, , Puerto Rico

Site Status

Research and Cardiovascular Corp.

Ponce, , Puerto Rico

Site Status

Ivanovo Regional Healthcare Institution Cardiology Dispensary

Ivanovo, Ivanovo Oblast, Russia

Site Status

Russian Cardiology Research and Production Complex

Moscow, Moscow, Russia

Site Status

Russian Medical Academy of Postgraduate Education

Moscow, Moscow, Russia

Site Status

Ryazan Regional Clinical Cardiological Dispensary

Ryazan, Ryazan Oblast, Russia

Site Status

Astarta Clinic

Saint Petersburg, Sankt-Peterburg, Russia

Site Status

Izhevsk City Clinical Hospital Number 9

Izhevsk, Udmurtiya Republic, Russia

Site Status

Chung Shan Medical University Hospital

Taichung, Taichung, Taiwan

Site Status

Mackay Memorial Hospital-Hsinchu

Hsinchu, , Taiwan

Site Status

Kaohsiung Medical University Hospital

Kaohsiung City, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Taipei Medical University Hospital

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Chang Gung Medical Foundation-Linkou Branch

Taoyuan District, , Taiwan

Site Status

Countries

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United States Argentina Brazil China India Israel Mexico Puerto Rico Russia Taiwan

References

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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.

Reference Type DERIVED
PMID: 40903131 (View on PubMed)

Borlaug 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.

Reference Type DERIVED
PMID: 40701669 (View on PubMed)

Packer 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.

Reference Type DERIVED
PMID: 40162940 (View on PubMed)

Kramer 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.

Reference Type DERIVED
PMID: 39566869 (View on PubMed)

Zile 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.

Reference Type DERIVED
PMID: 39556714 (View on PubMed)

Packer 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.

Reference Type DERIVED
PMID: 39555826 (View on PubMed)

Borlaug 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.

Reference Type DERIVED
PMID: 39551891 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://trials.lillytrialguide.com/en-US/trial/4deAJHqkMfFYm9JjtgeqTl

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

Other Identifiers

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I8F-MC-GPID

Identifier Type: OTHER

Identifier Source: secondary_id

17757

Identifier Type: -

Identifier Source: org_study_id

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