ObesityPhase 3SURMOUNT-4NCT04660643
A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight for the Maintenance of Weight Loss
A Phase 3 study testing Tirzepatide in people with Obesity and Overweight, run by Eli Lilly and Company at 70 sites in 5 countries.
Trial 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… 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
- 783 participants
- Where
- 70 sitesin 5 countries
- Study dates
- 29 Mar 2021to 18 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
- 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
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
70 sites in 5 countries.
70 sites in 5 countries
United States48 sites
The University of Texas Health Science Center at Houston
Bellaire, Texas, 77401
Capital Area Research, LLC
Camp Hill, Pennsylvania, 17011
University of North Carolina Medical Center
Chapel Hill, North Carolina, 27514
StudyMetrix Research
City of Saint Peters, Missouri, 63303
Aventiv Research Inc
Columbus, Ohio, 43213
Dallas Diabetes Research Center
Dallas, Texas, 75230
North Texas Endocrine Center
Dallas, Texas, 75231
Centennial Medical Group
Elkridge, Maryland, 21075
Lillestol Research
Fargo, North Dakota, 58104
Healthcare Research Network - Chicago
Flossmoor, Illinois, 60422
New West Physicians Clinical Research
Golden, Colorado, 80401
PharmQuest
Greensboro, North Carolina, 27408
Tribe Clinical Research, LLC
Greenville, South Carolina, 29607
Clinical Investigation Specialists
Gurnee, Illinois, 60031
East-West Medical Research Institute
Honolulu, Hawaii, 96814
Biopharma Informatic, LLC
Houston, Texas, 77043
MedStar Health Research Institute (MedStar Physician Based Research Network)
Hyattsville, Maryland, 20782
Rocky Mountain Clinical Research
Idaho Falls, Idaho, 83404
Midwest Institute For Clinical Research
Indianapolis, Indiana, 46260
Care Partners Clinical Research
Jacksonville, Florida, 32277
Glacier View Research Institute - Endocrinology
Kalispell, Montana, 59901
Scripps Memorial Hospital La Jolla
La Jolla, California, 92037
National Research Institute - Wilshire
Los Angeles, California, 90057
L-MARC Research Center
Louisville, Kentucky, 40213
South Florida Clinical Research Institute
Margate, Florida, 33063
ActivMed Practices and Research
Methuen, Massachusetts, 01844
Optumcare Colorado Springs - Monument
Monument, Colorado, 80132
American Health Network of Indiana, LLC - New Albany
New Albany, Indiana, 47150
Weill Cornell Medical College
New York, New York, 10065
Health Research of Hampton Roads, Inc.
Newport News, Virginia, 23606
Intend Research, LLC
Norman, Oklahoma, 73069
North Hills Family Medicine/North Hills Medical Research
North Richland Hills, Texas, 76180
Renstar Medical Research
Ocala, Florida, 34470
Capital Clinical Research Center
Olympia, Washington, 98502
National Research Institute
Panorama City, California, 91402
Cahaba Research
Pelham, Alabama, 35124
Summit Research Network
Portland, Oregon, 97210
Rainier Clinical Research Center
Renton, Washington, 98057
Endocrine Research Solutions, Inc.
Roswell, Georgia, 30076
Clinical Trials of Texas, Inc.
San Antonio, Texas, 78229
Artemis Institute for Clinical Research
San Diego, California, 92103
ForCare Clinical Research
Tampa, Florida, 33613
Northwest Houston Heart Center
Tomball, Texas, 77375
Cotton O'Neil Clinic
Topeka, Kansas, 66606
Arcturus Healthcare , PLC, Troy Internal Medicine Research Division
Troy, Michigan, 48098
University Clinical Investigators, Inc.
Tustin, California, 92780
SKY Clinical Research Network Group-Blake
Union City, Georgia, 30291
Wake Forest University Baptist Medical Center (WFUBMC)
Winston-Salem, North Carolina, 27157
Brazil8 sites
Centro de Pesquisa Sao Lucas
Campinas, São Paulo, 13034-685
Cline Research Center
Curitiba, Paraná, 80030-480
Núcleo de Pesquisa Clínica do Rio Grande do Sul
Porto Alegre, Rio Grande do Sul, 90430-001
IBPClin - Instituto Brasil de Pesquisa Clínica
Rio de Janeiro, 22241-180
ISPEM - Instituto São José dos Campos em Pesquisas Médicas
São José dos Campos, São Paulo, 12243-280
BR Trials - Ensaios Clinicos e Consultoria
São Paulo, São Paulo, 03325-050
CPQuali Pesquisa Clínica
São Paulo, 01228-000
CEDOES
Vitória, Espírito Santo, 29055450
Argentina7 sites
Mautalen Salud e Investigación
Buenos Aires, Ciudad Autónoma de Buenos Aire, C1128AAF
Asociación de Beneficencia Hospital Sirio Libanés
Buenos Aires, C1419AHN
CEDIC
CABA, Buenos Aires, C1060ABN
Centro Médico Viamonte
CABA, Buenos Aires, C1120AAC
Centro Medico Dr Laura Maffei Investigacion Clinica Aplicada
Ciudad Autonoma de Buenos Aire, Ciudad Autónoma de Buenos Aire, C1425AGC
Stat Research S.A.
Ciudad Autónoma de Buenos Aire, Buenos Aires, C1023AAB
Instituto Médico Catamarca IMEC
Rosario, Santa Fe Province, 2000
Taiwan4 sites
Chung Shan Medical University Hospital
Taichung, 402
China Medical University Hospital
Taichung, 40447
National Cheng-Kung Uni. Hosp.
Tainan, 704
National Taiwan University Hospital
Taipei, 10002
Puerto Rico3 sites
Centro de Endocrinologia Alcantara Gonzalez
Bayamón, 00959
Private Practice Dr. Martha Gomez Cuellar
San Juan, 00921
Wellness clinical Research Vega Baja
Vega Baja, 00694
About this study
Official title: Efficacy and Safety of Tirzepatide Once Weekly Versus Placebo for Maintenance of Weight Loss in Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight With Weight-Related Comorbidities: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-4)
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).
- Conditions
- Obesity, Overweight
- Being tested
- Tirzepatide, Placebo
- Keywords
- Metabolism and Nutrition Disorder, Prediabetes
- Medical subject headings
- Obesity, Overweight, Nutrition Disorders, Prediabetic State
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 group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Tirzepatide |
| Tirzepatide MTD | Experimental | Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks. Receives: Drug: Tirzepatide |
| Placebo | Placebo comparator | Participants received weekly doses of placebo SC for 52 weeks. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Randomization (Week 36), Week 88
Secondary outcomes (25)
Percent Change From Randomization in Body Weight at Week 64
LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + treatment + time + treatment*time (Type III sum of squares) as variables.
Measured: Randomization (Week 36), Week 64
Change From Randomization in Body Weight
LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + treatment + time + treatment*time (Type III sum of squares) as variables.
Measured: Randomization (Week 36), Week 88
Change From Randomization in Waist Circumference
LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (< 10%, >= 10%) + treatment + time + treatment*time (Type III sum of squares) as variables.
Measured: Randomization (Week 36), Week 88
Change From Randomization in Body Mass Index (BMI)
LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + treatment + time + treatment*time (Type III sum of squares) as variables.
Measured: Randomization (Week 36), Week 88
Change From Randomization in Fasting Glucose
LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (< 10%, >= 10%) + treatment + time + treatment*time (Type III sum of squares) as variables.
Measured: Randomization (Week 36), Week 88
Change From Randomization in Hemoglobin A1c (HbA1c)
LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (< 10%, >= 10%) + treatment + time + treatment*time (Type III sum of squares) as variables.
Measured: Randomization (Week 36), Week 88
Percent Change From Randomization in Fasting Insulin
LS mean was analysed by MMRM model with log(actual measurement/randomization) = log (randomization) + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (< 10%, >= 10%) + treatment + time + treatment*time (Type III sum of squares) as variables.
Measured: Randomization (Week 36), Week 88
Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA))
LS mean was analysed by MMRM model with log(actual measurement/randomization) = log (randomization) + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (< 10%, >= 10%) + treatment + time + treatment*time (Type III sum of squares) as variables.
Measured: Randomization (Week 36), Week 88
Change From Randomization in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
LS mean change was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + Weight Loss at Week 36 (< 10%, >= 10%) + treatment + time + treatment*time (Type III sum of squares) as variables.
Measured: Randomization (Week 36), Week 88
Change From Randomization in Short Form 36 Version 2 Health Survey (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 analysed by analysis of covariance (ANCOVA) model with randomization + analysis Country + sex + weight loss at Week 36 (< 10%, >= 10%) + IWRS MTD at Week 36 + treatment (type III sum of squares) as variables.
Measured: Randomization (Week 36), Week 88
Change From Randomization 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 analysed by ANCOVA model with randomization + analysis Country + sex + weight loss at Week 36 (< 10%, >= 10%) + IWRS MTD at Week 36 + treatment (type III sum of squares) as variables.
Measured: Randomization (Week 36), Week 88
Percentage of Participants Who Maintain at Least 80% of the Body Weight Lost During the Open-Label Lead-In Period
Percentage of Participants Who Maintain at least 80% of the Body Weight Lost During the Open-Label Lead-In Period was analysed by Logistic regression model with missing value imputed by MMRM at week 88. Missing values were imputed by predictions using observed data in the efficacy analysis set from the same treatment group through an MMRM analysis model for post-baseline measures with Baseline + Analysis Country + Sex + IWRS MTD at Week 36 + randomization + Treatment + Time + Treatment*Time as variables.
Measured: Week 88
Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction From Baseline
Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction from baseline was analysed by Logistic regression model with missing value imputed by MMRM at week 88. Missing values were imputed by predictions using observed data in the efficacy analysis set from the same treatment group through an MMRM analysis model for post-baseline measures with Baseline + Analysis Country + Sex + IWRS MTD at Week 36 + randomization + Treatment + Time + Treatment*Time as variables.
Measured: Baseline (Week 0) to Week 88
Time to First Occurrence of Participants Returning to >95% Baseline Weight for Those Who Lost ≥5% During the Open-Label Lead-In Period
Time to first occurrence of participants returning to >95% baseline weight for those who lost ≥5% during the open-label lead-in period.
Measured: Randomization (Week 36) to Week 88
Change From Baseline in BMI
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + BMI at randomization (kg/m^2) + treatment + time + treatment*time (Type III sum of squares) as variables.
Measured: Baseline (Week 0), Week 88
Change From Baseline in Body Weight
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + body weight at randomization (kg) + treatment + time + treatment*time (Type III sum of squares) as variables.
Measured: Baseline (Week 0), Week 88
Percent Change From Baseline in Body Weight
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + body weight at randomization (kg) + treatment + time + treatment*time (Type III sum of squares) as variables.
Measured: Baseline (Week 0), Week 88
Change From Baseline in Waist Circumference
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (< 10%, >= 10%) + treatment + time + treatment*time (Type III sum of squares) as variables.
Measured: Baseline (Week 0), Week 88
Change From Baseline in Fasting Glucose
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (< 10%, >= 10%) + treatment + time + treatment*time (Type III sum of squares) as variables.
Measured: Baseline (Week 0), Week 88
Change From Baseline in HbA1c
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (< 10%, >= 10%) + treatment + time + treatment*time (Type III sum of squares) as variables.
Measured: Baseline (Week 0), Week 88
Percent Change From Baseline in Fasting Insulin
LS mean was analysed by MMRM model with log(actual measurement/baseline) = log (baseline) + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (< 10%, >= 10%) + treatment + time + treatment*time (Type III sum of squares) as variables.
Measured: Baseline (Week 0), Week 88
Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs)
LS mean was analysed by MMRM model with log(actual measurement/baseline) = log (baseline) + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (< 10%, >= 10%) + treatment + time + treatment*time (Type III sum of squares) as variables.
Measured: Baseline (Week 0), Week 88
Change From Baseline in SBP, DBP
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + Weight Loss at Week 36 (< 10%, >= 10%) + treatment + time + treatment*time (Type III sum of squares) as variables.
Measured: Baseline (Week 0), Week 88
Change From Baseline in 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 analysed by analysis of covariance (ANCOVA) model with randomization + analysis Country + sex + weight loss at Week 36 (< 10%, >= 10%) + IWRS MTD at Week 36 + treatment (type III sum of squares) as variables.
Measured: Baseline (Week 0), Week 88
Change From Baseline in 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 analysed by ANCOVA model with baseline + analysis Country + sex + weight loss at Week 36 (< 10%, >= 10%) + IWRS MTD at Week 36 + treatment (type III sum of squares) as variables.
Measured: Baseline (Week 0), Week 88
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2020
- Study start29 Mar 2021
- Primary completion25 Apr 2023
- Study completion18 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 783 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04660643
- Sponsor's protocol ID
- 17247
- Other IDs
- I8F-MC-GPHN
- Acronym
- SURMOUNT-4
- Status last verified
- May 2024
- First submitted
- 1 Dec 2020
- Last updated
- 22 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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 41885866Almandoz 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 41640675Horn 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. 2026 Feb 1;186(2):157-167. doi: 10.1001/jamainternmed.2025.6112.
PubMed 41284285Li 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 41187013Gibble 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.
PubMed 40903801Gourgari 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 40717199Horn 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.
PubMed 39800653Aronne 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.
PubMed 38078870
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Tirzepatide Once Weekly Versus Placebo for Maintenance of Weight Loss in Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight With Weight-Related Comorbidities: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-4)
- ClinicalTrials.gov ID
- NCT04660643
- Acronym / sponsor ID
- SURMOUNT-4 / 17247
- Conditions
- Obesity, Overweight
- Keywords
- Metabolism and Nutrition Disorder, Prediabetes
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 783 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- 29 Mar 2021 (actual)
- Primary completion
- 25 Apr 2023 (actual)
- Study completion
- 18 May 2023 (actual)
- First posted
- 9 Dec 2020 (actual)
- Results
- Posted 22 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Tirzepatide (lead-in) | Experimental | Drug: TirzepatideParticipants 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. |
| Tirzepatide MTD | Experimental | Drug: TirzepatideParticipants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks. |
| Placebo | Placebo comparator | Other: PlaceboParticipants received weekly doses of placebo SC for 52 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TirzepatideAlso: LY3298176Administered SC | Drug | Tirzepatide (lead-in), Tirzepatide MTD |
| PlaceboAdministered SC | Other | Placebo |
Primary outcome
Percent Change From Randomization in Body Weight at Week 88
Time frame: Randomization (Week 36), 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.
25 secondary outcomes
Percent Change From Randomization in Body Weight at Week 64
Time frame: Randomization (Week 36), Week 64
Change From Randomization in Body Weight
Time frame: Randomization (Week 36), Week 88
Change From Randomization in Waist Circumference
Time frame: Randomization (Week 36), Week 88
Change From Randomization in Body Mass Index (BMI)
Time frame: Randomization (Week 36), Week 88
Change From Randomization in Fasting Glucose
Time frame: Randomization (Week 36), Week 88
Change From Randomization in Hemoglobin A1c (HbA1c)
Time frame: Randomization (Week 36), Week 88
Percent Change From Randomization in Fasting Insulin
Time frame: Randomization (Week 36), Week 88
Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA))
Time frame: Randomization (Week 36), Week 88
Change From Randomization in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
Time frame: Randomization (Week 36), Week 88
Change From Randomization in Short Form 36 Version 2 Health Survey (SF 36v2) Acute Form - Physical Functioning Domain Score
Time frame: Randomization (Week 36), Week 88
Change From Randomization in Impact of Weight on Quality of Life Lite Clinical Trials Version (IWQOL-Lite-CT) - Physical Function Composite Score
Time frame: Randomization (Week 36), Week 88
Percentage of Participants Who Maintain at Least 80% of the Body Weight Lost During the Open-Label Lead-In Period
Time frame: Week 88
Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction From Baseline
Time frame: Baseline (Week 0) to Week 88
Time to First Occurrence of Participants Returning to >95% Baseline Weight for Those Who Lost ≥5% During the Open-Label Lead-In Period
Time frame: Randomization (Week 36) to Week 88
Change From Baseline in BMI
Time frame: Baseline (Week 0), Week 88
Change From Baseline in Body Weight
Time frame: Baseline (Week 0), Week 88
Percent Change From Baseline in Body Weight
Time frame: Baseline (Week 0), Week 88
Change From Baseline in Waist Circumference
Time frame: Baseline (Week 0), Week 88
Change From Baseline in Fasting Glucose
Time frame: Baseline (Week 0), Week 88
Change From Baseline in HbA1c
Time frame: Baseline (Week 0), Week 88
Percent Change From Baseline in Fasting Insulin
Time frame: Baseline (Week 0), Week 88
Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs)
Time frame: Baseline (Week 0), Week 88
Change From Baseline in SBP, DBP
Time frame: Baseline (Week 0), Week 88
Change From Baseline in SF 36v2 Acute Form - Physical Functioning Domain Score
Time frame: Baseline (Week 0), Week 88
Change From Baseline in IWQOL-Lite-CT - Physical Function Composite Score
Time frame: Baseline (Week 0), Week 88
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41885866Galindo 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.
- Derived from this study: PubMed 41640675Almandoz 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.
- Derived from this study: PubMed 41284285Horn 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. 2026 Feb 1;186(2):157-167. doi: 10.1001/jamainternmed.2025.6112.
- Derived from this study: PubMed 41187013Li 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.
- Derived from this study: PubMed 40903801Gibble 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.
- Derived from this study: PubMed 40717199Gourgari 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.
- Derived from this study: PubMed 39800653Horn 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.
- Derived from this study: PubMed 38078870Aronne 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.
- A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight for the Maintenance of Weight Loss (SURMOUNT-4)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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) study director
Eli Lilly and Company
70 sites in 5 countries: see every site and its status.
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 70 sites in 5 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 22 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 70 sites in United States, Brazil, Argentina, Taiwan, 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 22 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 Randomization in Body Weight at Week 88 (time frame: Randomization (Week 36), Week 88). 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 NCT04660643, which also lists 8 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 22 May 2024.