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ObesityPhase 3SURMOUNT-3NCT04657016

A Study of Tirzepatide (LY3298176) In Participants After A Lifestyle Weight Loss Program

A Phase 3 study testing Tirzepatide in people with Obesity and Overweight, run by Eli Lilly and Company at 65 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a study of tirzepatide in participants with obesity. The purpose of this study is to learn more about how tirzepatide maintains body weight or adds to weight loss after an intensive lifestyle modification program. The study will last about 2 years (29 visits). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Obesity, Overweight
What is being tested?
Tirzepatide
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
579 participants
Where
65 sitesin 4 countries
Study dates
29 Mar 2021to 12 May 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Have a body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 and previously diagnosed with at least 1 of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease
  • History of at least one unsuccessful dietary effort to lose body weight

Who cannot join

  • 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

Trial locations and contacts

65 sites in 4 countries.

65 sites in 4 countries

United States45 sites
  • American Health Network of IN, LLC

    Avon, Indiana, 46123

  • The National Diabetes & Obesity Research Institute

    Biloxi, Mississippi, 39532

  • Elite Clinical Trials

    Blackfoot, Idaho, 83221

  • Holston Medical Group

    Bristol, Tennessee, 37620

  • University of North Carolina Medical Center

    Chapel Hill, North Carolina, 27514

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44122

  • Clinical Research of South Florida

    Coral Gables, Florida, 33134

  • Dallas Diabetes Research Center

    Dallas, Texas, 75230

  • Evanston Premier Healthcare Research LLC

    Evanston, Illinois, 60201

  • American Health Network of IN, LLC

    Franklin, Indiana, 46131

  • PharmQuest

    Greensboro, North Carolina, 27408

  • Tribe Clinical Research, LLC

    Greenville, South Carolina, 29607

  • Juno Research

    Houston, Texas, 77040

  • National Research Institute - Huntington Park

    Huntington Park, California, 90255

  • Detweiler Family Medicine & Associates

    Lansdale, Pennsylvania, 19446

  • Palm Research Center Sunset

    Las Vegas, Nevada, 89148

  • National Research Institute - Wilshire

    Los Angeles, California, 90057

  • Tandem Clinical Research,LLC

    Marrero, Louisiana, 70072

  • Solaris Clinical Research

    Meridian, Idaho, 83646

  • Southern Endocrinology Associates

    Mesquite, Texas, 75149

  • New Horizon Research Center

    Miami, Florida, 33165

  • Catalina Research Institute, LLC

    Montclair, California, 91763

  • American Health Network of IN, LLC

    Muncie, Indiana, 47304

  • Vanderbilt Health One Hundred Oaks

    Nashville, Tennessee, 37204

  • Health Research of Hampton Roads, Inc.

    Newport News, Virginia, 23606

  • Intend Research, LLC

    Norman, Oklahoma, 73069

  • Quality Clinical Research

    Omaha, Nebraska, 68114

  • Penn Medicine: University of Pennsylvania Health System

    Philadelphia, Pennsylvania, 19104

  • Preferred Primary Care Physicians, Preferred Clinical Research-St. Clair

    Pittsburgh, Pennsylvania, 15243

  • Summit Research Network

    Portland, Oregon, 97210

  • Elite Clinical Trials

    Rexburg, Idaho, 83440

  • Rochester Clinical Research, Inc.

    Rochester, New York, 14609

  • Texas Diabetes & Endocrinology, P.A.

    Round Rock, Texas, 78681

  • National Research Institute (NRI) - Santa Ana

    Santa Ana, California, 92704

  • Consano Clinical Research, LLC

    Shavano Park, Texas, 78231

  • Encompass Clinical Research

    Spring Valley, California, 91978

  • Clinvest Research LLC

    Springfield, Missouri, 65810

  • Precision Clinical Research

    Sunrise, Florida, 33351

  • MultiCare Institute for Research & Innovation

    Tacoma, Washington, 98405

  • Clinical Research of West Florida

    Tampa, Florida, 33606

  • Cotton O'Neil Mulvane

    Topeka, Kansas, 66606

  • Diablo Clinical Research, Inc.

    Walnut Creek, California, 94598

  • Chase Medical Research, LLC

    Waterbury, Connecticut, 06708

  • Metabolic Research Institute, Inc.

    West Palm Beach, Florida, 33401

  • Wake Forest University Baptist Medical Center (WFUBMC)

    Winston-Salem, North Carolina, 27157

Other trials in United States

Argentina9 sites
  • Glenny Corp

    Buenos Aires, Ciudad Autónoma de Buenos Aire, 1430

  • Instituto Médico Especializado (IME)

    Buenos Aires, 1405

  • CEMEDIAB

    C.a.b.a., Ciudad Autónoma de Buenos Aire, C1205AAO

  • Centro Médico Viamonte

    CABA, Buenos Aires, C1120AAC

  • Investigaciones Medicas Imoba Srl

    CABA, Buenos Aires, C1179AAB

  • Instituto Centenario

    CABA, Buenos Aires, C1204AAD

  • Centro de Investigaciones Metabólicas (CINME)

    Ciudad Autónoma de Buenos Aire, Buenos Aires, 1056

  • Stat Research S.A.

    Ciudad Autónoma de Buenos Aire, Buenos Aires, C1023AAB

  • Sanatorio Norte

    Santiago del Estero, 4200

Other trials in Argentina

Brazil8 sites
  • Cline Research Center

    Curitiba, Paraná, 80030-480

  • Quanta Diagnóstico e Terapia

    Curitiba, Paraná, 80040-110

  • IBPClin - Instituto Brasil de Pesquisa Clínica

    Rio de Janeiro, 22241-180

  • CPCLIN

    São Paulo, São Paulo, 01228-200

  • BR Trials - Ensaios Clinicos e Consultoria

    São Paulo, São Paulo, 03325-050

  • CPQuali Pesquisa Clínica

    São Paulo, 01228-000

  • CEPIC - Centro Paulista de Investigação Clínica

    São Paulo, 04266-010

  • CEDOES

    Vitória, Espírito Santo, 29055450

Other trials in Brazil

Puerto Rico3 sites
  • Advanced Clinical Research, LLC

    Bayamón, 00961

  • Manati Center for Clinical Research

    Manati, 00674

  • Ponce Medical School Foundation Inc.

    Ponce, 00716

Other trials in Puerto Rico

About this study

Official title: Efficacy and Safety of Tirzepatide Once Weekly Versus Placebo After an Intensive Lifestyle Program in Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight With Weight-Related Comorbidities: A Randomized, Double Blind, Placebo-Controlled Trial (SURMOUNT-3)

This is a study of tirzepatide in participants with obesity. The purpose of this study is to learn more about how tirzepatide maintains body weight or adds to weight loss after an intensive lifestyle modification program. The study will last about 2 years (29 visits).

Conditions
Obesity, Overweight
Being tested
Tirzepatide, Placebo
Keywords
Diet, Exercise, Metabolism and Nutrition Disorder, Behavioral Modification
Medical subject headings
Obesity, Overweight, Motor Activity, Nutrition Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TirzepatideDrug

    Also called LY3298176

    Administered SC

  • PlaceboOther

    Administered SC

Study groups in NCT04657016
Study groupRoleWhat they receive
TirzepatideExperimentalParticipants received weekly doses of tirzepatide subcutaneously (SC) for 72 weeks, starting at 2.5 milligrams (mg) for 4 weeks. Subsequently, the dose was increased by 2.5 mg every 4 weeks up to the maximum tolerated dose (MTD) of either 10 mg or 15 mg.
Receives: Drug: Tirzepatide
PlaceboPlacebo comparatorParticipants received matching placebo SC once weekly (QW).
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent Change From Baseline in Body Weight

    Percent change from baseline in body weight. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, 72 Weeks

  2. Percentage of Participants With Greater Than or Equal to (≥) 5% Body Weight Reduction

    Percentage of participants with ≥5% body weight reduction was analysed by Logistic regression model using imputed data with baseline body weight, Analysis Country, Sex, Treatment as factors.

    Measured: Week 72

Secondary outcomes (20)
  1. Percentage of Participants Who Maintain ≥80% of the Body Weight Lost During Intensive Lifestyle Program

    Percentage of participants who maintain ≥80% of the body weight lost during intensive lifestyle program was analysed by logistic regression model using imputed data with baseline body weight, analysis country, sex, treatment as factors.

    Measured: 72 Weeks

  2. Percentage of Participants Who Achieve ≥10%Body Weight Reduction

    Percentage of participants who achieve ≥10% body weight reduction was analysed by logistic regression model using imputed data with baseline body weight, analysis country, sex, treatment as factors.

    Measured: 72 Weeks

  3. Percentage of Participants Who Achieve ≥15% Body Weight Reduction

    Percentage of participants who achieve ≥15% body weight reduction was analysed by logistic regression model using imputed data with baseline body weight, analysis country, sex, treatment as factors.

    Measured: 72 Weeks

  4. Percentage of Participants Who Achieve ≥20% Body Weight Reduction

    Percentage of participants who achieve ≥20% body weight reduction was analysed by logistic regression model using imputed data with baseline body weight, analysis country, sex, treatment as factors.

    Measured: 72 Weeks

  5. Change From Baseline in Waist Circumference

    Change from baseline in waist circumference. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, 72 Weeks

  6. Change From Baseline in Body Weight

    Change from baseline in body weight. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, 72 Weeks

  7. Change From Baseline in Body Mass Index (BMI)

    Change from baseline in BMI. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, 72 Weeks

  8. Change From Baseline in Systolic Blood Pressure (SBP)

    Change from baseline in SBP. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, 72 Weeks

  9. Change From Baseline in Diastolic Blood Pressure (DBP)

    Change from baseline in DBP. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, 72 Weeks

  10. Percent Change From Baseline in Total Cholesterol

    Percent change from baseline in total cholesterol. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, 72 Weeks

  11. Percent Change From Baseline in High Density Lipoprotein (HDL) Cholesterol

    Percent change from baseline in HDL cholesterol. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, 72 Weeks

  12. Percent Change From Baseline in Low Density Lipoprotein (LDL) Cholesterol

    Percent change from baseline in LDL cholesterol. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, 72 Weeks

  13. Percent Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol

    Percent change from baseline in VLDL cholesterol. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, 72 Weeks

  14. Percent Change From Baseline in Triglycerides

    Percent change from baseline in triglycerides. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, 72 Weeks

  15. Percent Change From Baseline in Free Fatty Acids

    Percent change from baseline in free fatty acids. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, 72 Weeks

  16. Change From Baseline in Fasting Glucose

    Change from baseline in fasting glucose. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, 72 Weeks

  17. Change From Baseline in Hemoglobin A1c (HbA1c)

    HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, 72 Weeks

  18. Percent Change From Baseline in Fasting Insulin

    Percent change from baseline in fasting insulin. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment*Time (Type III sum of squares).

    Measured: Baseline, 72 Weeks

  19. Change From Baseline in Short Form 36 Version 2 Health Survey Version 2 (SF 36v2) Acute Form Physical Functioning Domain Score

    The SF-36v2 acute form assesses health-related quality of life (HRQoL) on 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The Physical-Functioning domain assesses limitations due to health "now" and consists of 10-items, each rated on a 3-point Likert scale. Scoring of the domain is norm-based and presented in the form of T-scores, with a mean of 50 and standard deviation of 10; higher scores indicate better levels of function. Range cannot be specified in norm-based scores.

    LS mean was determined using analysis of covariance (ANCOVA) model using Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment (Type III sum of squares) as variables.

    Measured: Baseline, 72 Weeks

  20. Change From Baseline in Impact of Weight on Quality of Life Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score

    The IWQOL Lite-CT consists of 20 items, assessing 2 primary domains of obesity related HRQoL: Physical (7 items) and Psychosocial (13 items). A 5-item subset of the Physical domain - the Physical Function composite - is also supported. Items in the Physical Function composite describe physical impacts related to general and specific physical activities. All items in the physical domain are rated on either a 5-point frequency ("never" to "always") scale or a 5-point truth ("not at all true" to "completely true") scale. Total score of IWQOL-Lite-CT composite ranges from 0 to 100, with higher scores reflecting better health-related quality of life.

    LS mean was determined using ANCOVA model with Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment (Type III sum of squares) as variables.

    Measured: Baseline, 72 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Dec 2020
  2. Study start29 Mar 2021
  3. Primary completion20 Apr 2023
  4. Study completion12 May 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
579 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04657016
Sponsor's protocol ID
17246
Other IDs
I8F-MC-GPHM
Acronym
SURMOUNT-3
Status last verified
May 2024
First submitted
1 Dec 2020
Last updated
16 May 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Plan Description: 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.

Publications

  • Galindo RJ, Gudzune KA, Look M, Lee CJ, Benabbad I, Cao D, Meng Q, Mojdami D. Weight Changes With Tirzepatide and Concomitant Weight-Inducing Medications: Post Hoc Analysis of Randomized Clinical Trials. JAMA Netw Open. 2026 Mar 2;9(3):e263274. doi: 10.1001/jamanetworkopen.2026.3274.

    PubMed 41885866
  • 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.

    PubMed 41640675
  • Wadden TA, Oquendo MA, Kushner RF, Cao D, Karanikas CA, Kechter A, Murphy MA. Psychiatric Safety of Tirzepatide in People With Obesity and No Known Major Psychopathology: A Post Hoc Analysis of SURMOUNT. Obesity (Silver Spring). 2026 Mar;34(3):565-578. doi: 10.1002/oby.70122. Epub 2026 Jan 15.

    PubMed 41537305
  • 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.

    PubMed 41187013
  • 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.

    PubMed 40717199
  • Wadden TA, Chao AM, Machineni S, Kushner R, Ard J, Srivastava G, Halpern B, Zhang S, Chen J, Bunck MC, Ahmad NN, Forrester T. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nat Med. 2023 Nov;29(11):2909-2918. doi: 10.1038/s41591-023-02597-w. Epub 2023 Oct 15.

    PubMed 37840095

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tirzepatide in people with Obesity and Overweight, run by Eli Lilly and Company at 65 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 65 sites in United States, Argentina, Brazil, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in Body Weight (time frame: Baseline, 72 Weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04657016, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2024.

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