NCT04660643

Brief Summary

This was a study of tirzepatide in participants with obesity or overweight. The main purpose was to learn more about how tirzepatide maintained body weight loss. The study had two phases: a lead-in phase in which all participants took tirzepatide and a treatment phase in which participants either continued tirzepatide or switched to placebo. The study lasted about 2 years (25 visits).

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
783

participants targeted

Target at P75+ for phase_3 obesity

Timeline
Completed

Started Mar 2021

Geographic Reach
5 countries

70 active sites

Status
completed

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

December 1, 2020

Completed
8 days until next milestone

First Posted

Study publicly available on registry

December 9, 2020

Completed
4 months until next milestone

Study Start

First participant enrolled

March 29, 2021

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 25, 2023

Completed
23 days until next milestone

Study Completion

Last participant's last visit for all outcomes

May 18, 2023

Completed
1 year until next milestone

Results Posted

Study results publicly available

May 22, 2024

Completed
Last Updated

May 22, 2024

Status Verified

May 1, 2024

Enrollment Period

2.1 years

First QC Date

December 1, 2020

Results QC Date

April 25, 2024

Last Update Submit

May 21, 2024

Conditions

Keywords

Metabolism and Nutrition DisorderPrediabetes

Outcome Measures

Primary Outcomes (1)

  • Percent Change From Randomization in Body Weight at Week 88

    Least square (LS) mean was analysed by mixed model repeated measures (MMRM) model with randomization + analysis country + sex + interactive web response system (IWRS) MTD at Week 36 + treatment + time + treatment\*time (Type III sum of squares) as variables.

    Randomization (Week 36), Week 88

Secondary Outcomes (25)

  • Percent Change From Randomization in Body Weight at Week 64

    Randomization (Week 36), Week 64

  • Change From Randomization in Body Weight

    Randomization (Week 36), Week 88

  • Change From Randomization in Waist Circumference

    Randomization (Week 36), Week 88

  • Change From Randomization in Body Mass Index (BMI)

    Randomization (Week 36), Week 88

  • Change From Randomization in Fasting Glucose

    Randomization (Week 36), Week 88

  • +20 more secondary outcomes

Study Arms (3)

Tirzepatide (lead-in)

EXPERIMENTAL

Participants received weekly doses of tirzepatide subcutaneously (SC) for 36 weeks, starting at 2.5 milligrams (mg) and increasing by 2.5 mg every 4 weeks, as tolerated, up to the maximum tolerated dose (MTD) of either 10 mg or 15 mg.

Drug: Tirzepatide

Tirzepatide MTD

EXPERIMENTAL

Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.

Drug: Tirzepatide

Placebo

PLACEBO COMPARATOR

Participants received weekly doses of placebo SC for 52 weeks.

Other: Placebo

Interventions

Administered SC

Also known as: LY3298176
Tirzepatide (lead-in)Tirzepatide MTD
PlaceboOTHER

Administered SC

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Body Mass Index (BMI) ≥30 kilograms per square meter (kg/m²), or ≥27 kg/m² and previous diagnosis with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease
  • History of at least one unsuccessful dietary effort to lose body weight

You may not qualify if:

  • Diabetes mellitus
  • Change in body weight greater than 5 kg within 3 months prior to starting study
  • Obesity induced by other endocrinologic disorders or monogenetic or syndromic forms of obesity
  • History of pancreatitis
  • Family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2)
  • History of significant active or unstable major depressive disorder (MDD) or other severe psychiatric disorder within the last 2 years
  • Any lifetime history of a suicide attempt

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (70)

Cahaba Research

Pelham, Alabama, 35124, United States

Location

Scripps Memorial Hospital La Jolla

La Jolla, California, 92037, United States

Location

National Research Institute - Wilshire

Los Angeles, California, 90057, United States

Location

National Research Institute

Panorama City, California, 91402, United States

Location

Artemis Institute for Clinical Research

San Diego, California, 92103, United States

Location

University Clinical Investigators, Inc.

Tustin, California, 92780, United States

Location

New West Physicians Clinical Research

Golden, Colorado, 80401, United States

Location

Optumcare Colorado Springs - Monument

Monument, Colorado, 80132, United States

Location

Care Partners Clinical Research

Jacksonville, Florida, 32277, United States

Location

South Florida Clinical Research Institute

Margate, Florida, 33063, United States

Location

Renstar Medical Research

Ocala, Florida, 34470, United States

Location

ForCare Clinical Research

Tampa, Florida, 33613, United States

Location

Endocrine Research Solutions, Inc.

Roswell, Georgia, 30076, United States

Location

SKY Clinical Research Network Group-Blake

Union City, Georgia, 30291, United States

Location

East-West Medical Research Institute

Honolulu, Hawaii, 96814, United States

Location

Rocky Mountain Clinical Research

Idaho Falls, Idaho, 83404, United States

Location

Healthcare Research Network - Chicago

Flossmoor, Illinois, 60422, United States

Location

Clinical Investigation Specialists

Gurnee, Illinois, 60031, United States

Location

Midwest Institute For Clinical Research

Indianapolis, Indiana, 46260, United States

Location

American Health Network of Indiana, LLC - New Albany

New Albany, Indiana, 47150, United States

Location

Cotton O'Neil Clinic

Topeka, Kansas, 66606, United States

Location

L-MARC Research Center

Louisville, Kentucky, 40213, United States

Location

Centennial Medical Group

Elkridge, Maryland, 21075, United States

Location

MedStar Health Research Institute (MedStar Physician Based Research Network)

Hyattsville, Maryland, 20782, United States

Location

ActivMed Practices and Research

Methuen, Massachusetts, 01844, United States

Location

Arcturus Healthcare , PLC, Troy Internal Medicine Research Division

Troy, Michigan, 48098, United States

Location

StudyMetrix Research

City of Saint Peters, Missouri, 63303, United States

Location

Glacier View Research Institute - Endocrinology

Kalispell, Montana, 59901, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

University of North Carolina Medical Center

Chapel Hill, North Carolina, 27514, United States

Location

PharmQuest

Greensboro, North Carolina, 27408, United States

Location

Wake Forest University Baptist Medical Center (WFUBMC)

Winston-Salem, North Carolina, 27157, United States

Location

Lillestol Research

Fargo, North Dakota, 58104, United States

Location

Aventiv Research Inc

Columbus, Ohio, 43213, United States

Location

Intend Research, LLC

Norman, Oklahoma, 73069, United States

Location

Summit Research Network

Portland, Oregon, 97210, United States

Location

Capital Area Research, LLC

Camp Hill, Pennsylvania, 17011, United States

Location

Tribe Clinical Research, LLC

Greenville, South Carolina, 29607, United States

Location

The University of Texas Health Science Center at Houston

Bellaire, Texas, 77401, United States

Location

Dallas Diabetes Research Center

Dallas, Texas, 75230, United States

Location

North Texas Endocrine Center

Dallas, Texas, 75231, United States

Location

Biopharma Informatic, LLC

Houston, Texas, 77043, United States

Location

North Hills Family Medicine/North Hills Medical Research

North Richland Hills, Texas, 76180, United States

Location

Clinical Trials of Texas, Inc.

San Antonio, Texas, 78229, United States

Location

Northwest Houston Heart Center

Tomball, Texas, 77375, United States

Location

Health Research of Hampton Roads, Inc.

Newport News, Virginia, 23606, United States

Location

Capital Clinical Research Center

Olympia, Washington, 98502, United States

Location

Rainier Clinical Research Center

Renton, Washington, 98057, United States

Location

CEDIC

CABA, Buenos Aires, C1060ABN, Argentina

Location

Centro Médico Viamonte

CABA, Buenos Aires, C1120AAC, Argentina

Location

Stat Research S.A.

Ciudad Autónoma de Buenos Aire, Buenos Aires, C1023AAB, Argentina

Location

Mautalen Salud e Investigación

Buenos Aires, Ciudad Autónoma de Buenos Aire, C1128AAF, Argentina

Location

Centro Medico Dr Laura Maffei Investigacion Clinica Aplicada

Ciudad Autonoma de Buenos Aire, Ciudad Autónoma de Buenos Aire, C1425AGC, Argentina

Location

Instituto Médico Catamarca IMEC

Rosario, Santa Fe Province, 2000, Argentina

Location

Asociación de Beneficencia Hospital Sirio Libanés

Buenos Aires, C1419AHN, Argentina

Location

CEDOES

Vitória, Espírito Santo, 29055450, Brazil

Location

Cline Research Center

Curitiba, Paraná, 80030-480, Brazil

Location

Núcleo de Pesquisa Clínica do Rio Grande do Sul

Porto Alegre, Rio Grande do Sul, 90430-001, Brazil

Location

Centro de Pesquisa Sao Lucas

Campinas, São Paulo, 13034-685, Brazil

Location

ISPEM - Instituto São José dos Campos em Pesquisas Médicas

São José dos Campos, São Paulo, 12243-280, Brazil

Location

BR Trials - Ensaios Clinicos e Consultoria

São Paulo, São Paulo, 03325-050, Brazil

Location

IBPClin - Instituto Brasil de Pesquisa Clínica

Rio de Janeiro, 22241-180, Brazil

Location

CPQuali Pesquisa Clínica

São Paulo, 01228-000, Brazil

Location

Centro de Endocrinologia Alcantara Gonzalez

Bayamón, 00959, Puerto Rico

Location

Private Practice Dr. Martha Gomez Cuellar

San Juan, 00921, Puerto Rico

Location

Wellness clinical Research Vega Baja

Vega Baja, 00694, Puerto Rico

Location

Chung Shan Medical University Hospital

Taichung, 402, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Cheng-Kung Uni. Hosp.

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Related Publications (7)

  • Almandoz JP, Pickett-Blakely O, Tewksbury C, Stefanski A, Gonsahn-Bollie S, Dimitriadis GK, Murro AL, Cao D, Meng Q, Neff LM. Nutritional status with tirzepatide in obesity: A post hoc analysis of the SURMOUNT-1-4 randomized clinical trials. Obes Pillars. 2026 Jan 23;17:100248. doi: 10.1016/j.obpill.2026.100248. eCollection 2026 Mar.

  • Horn DB, Linetzky B, Davies MJ, Laffin LJ, Wang H, Murphy MA, Zimner-Rapuch S, Lau E, Arad AD, Lee CJ. Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial. JAMA Intern Med. 2025 Nov 24:e256112. doi: 10.1001/jamainternmed.2025.6112. Online ahead of print.

  • Li X, Cao D, Sapin H, Wang F, Hunter Gibble T, Raibulet NK, Denning M, Kaplan LM. People With Lowest Physical Functioning Scores Showed Greatest Improvement After Tirzepatide Treatment. Obesity (Silver Spring). 2026 Jan;34(1):114-126. doi: 10.1002/oby.70067. Epub 2025 Nov 4.

  • Gibble TH, Cao D, Murphy M, Jouravskaya I, Liao B, Bays HE. Tirzepatide Associated With Improved Health-Related Quality of Life in Adults With Obesity or Overweight in SURMOUNT-4. Obesity (Silver Spring). 2025 Nov;33(11):2076-2092. doi: 10.1002/oby.70011. Epub 2025 Sep 3.

  • Gourgari E, Srivastava G, Kelly AS, Mojdami D, Cao D, Murphy MA, Karanikas CA, Lee CJ. Early-Onset Obesity and Tirzepatide Treatment: A Post Hoc Analysis of the SURMOUNT Clinical Trials. Obesity (Silver Spring). 2025 Sep;33(9):1668-1679. doi: 10.1002/oby.24348. Epub 2025 Jul 27.

  • Horn DB, Kahan S, Batterham RL, Cao D, Lee CJ, Murphy M, Gonsahn-Bollie S, Chigutsa F, Stefanski A, Dunn JP. Time to weight plateau with tirzepatide treatment in the SURMOUNT-1 and SURMOUNT-4 clinical trials. Clin Obes. 2025 Jun;15(3):e12734. doi: 10.1111/cob.12734. Epub 2025 Jan 12.

  • Aronne LJ, Sattar N, Horn DB, Bays HE, Wharton S, Lin WY, Ahmad NN, Zhang S, Liao R, Bunck MC, Jouravskaya I, Murphy MA; SURMOUNT-4 Investigators. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA. 2024 Jan 2;331(1):38-48. doi: 10.1001/jama.2023.24945.

Related Links

MeSH Terms

Conditions

ObesityOverweightNutrition DisordersPrediabetic State

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

OvernutritionNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsDiabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide ReceptorsReceptors, G-Protein-CoupledReceptors, Cell SurfaceMembrane ProteinsProteinsAmino Acids, Peptides, and ProteinsReceptors, Gastrointestinal HormoneReceptors, Peptide

Results Point of Contact

Title
Chief Medical Officer
Organization
Eli Lilly and Company

Study Officials

  • 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

    STUDY DIRECTOR

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

December 1, 2020

First Posted

December 9, 2020

Study Start

March 29, 2021

Primary Completion

April 25, 2023

Study Completion

May 18, 2023

Last Updated

May 22, 2024

Results First Posted

May 22, 2024

Record last verified: 2024-05

Data Sharing

IPD Sharing
Will share

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

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 Union (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.
More information

Locations