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Trial · Interventional

CompletedPhase 3Results postedRegistry data

A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight for the Maintenance of Weight Loss

Short name SURMOUNT-4

NCTNCT04660643 (opens ClinicalTrials.gov in a new tab)Other id17247Other idI8F-MC-GPHN
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
783 participants (actual)
Sponsor
Eli Lilly and Company · Industry
Design
Randomized · Double masking
Countries
5 countries

United States, Argentina, Brazil, Puerto Rico, Taiwan

Start
29 Mar 2021
Primary completion
25 Apr 2023
Completion
18 May 2023
First posted
9 Dec 2020
Last update posted
22 May 2024
Conditions
Obesity · Overweight

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2021202220232024
  1. Ph 3

    SURMOUNT-4

    NCT04660643

    29 Mar 2021 to 18 May 2023

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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).

Interventions

  • TirzepatideDrug
  • PlaceboOther

Arms3

  • Experimental

    Tirzepatide (lead-in)

    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.

  • Experimental

    Tirzepatide MTD

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

  • Placebo comparator

    Placebo

    Participants received weekly doses of placebo SC for 52 weeks.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Percent Change From Randomization in Body Weight at Week 88

    Time frame · Randomization (Week 36), Week 88

    Registry description

    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.

Secondary outcomes(20)

  1. Percent Change From Randomization in Body Weight at Week 64

    Time frame · Randomization (Week 36), Week 64

    Registry description

    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.

  2. Change From Randomization in Body Weight

    Time frame · Randomization (Week 36), Week 88

    Registry description

    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.

  3. Change From Randomization in Waist Circumference

    Time frame · Randomization (Week 36), Week 88

    Registry description

    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.

  4. Change From Randomization in Body Mass Index (BMI)

    Time frame · Randomization (Week 36), Week 88

    Registry description

    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.

  5. Change From Randomization in Fasting Glucose

    Time frame · Randomization (Week 36), Week 88

    Registry description

    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.

  6. Change From Randomization in Hemoglobin A1c (HbA1c)

    Time frame · Randomization (Week 36), Week 88

    Registry description

    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.

  7. Percent Change From Randomization in Fasting Insulin

    Time frame · Randomization (Week 36), Week 88

    Registry description

    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.

  8. 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

    Registry description

    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.

  9. Change From Randomization in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)

    Time frame · Randomization (Week 36), Week 88

    Registry description

    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.

  10. 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

    Registry description

    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.

  11. 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

    Registry description

    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.

  12. Percentage of Participants Who Maintain at Least 80% of the Body Weight Lost During the Open-Label Lead-In Period

    Time frame · Week 88

    Registry description

    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.

  13. Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction From Baseline

    Time frame · Baseline (Week 0) to Week 88

    Registry description

    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.

  14. 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

    Registry description

    Time to first occurrence of participants returning to \>95% baseline weight for those who lost ≥5% during the open-label lead-in period.

  15. Change From Baseline in BMI

    Time frame · Baseline (Week 0), Week 88

    Registry description

    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.

  16. Change From Baseline in Body Weight

    Time frame · Baseline (Week 0), Week 88

    Registry description

    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.

  17. Percent Change From Baseline in Body Weight

    Time frame · Baseline (Week 0), Week 88

    Registry description

    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.

  18. Change From Baseline in Waist Circumference

    Time frame · Baseline (Week 0), Week 88

    Registry description

    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.

  19. Change From Baseline in Fasting Glucose

    Time frame · Baseline (Week 0), Week 88

    Registry description

    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.

  20. Change From Baseline in HbA1c

    Time frame · Baseline (Week 0), Week 88

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeLeast squares mean· Randomization (Week 36), Week 88

Percent Change From Randomization in Body Weight at Week 88

GroupValue (percent change)Spread
Placebo14.80.53
Tirzepatide MTD-6.70.52
Secondary and other outcome results(7)
Secondary outcomeLeast squares mean· Randomization (Week 36), Week 64

Percent Change From Randomization in Body Weight at Week 64

GroupValue (percent change)Spread
Placebo9.90.38
Tirzepatide MTD-6.00.37
Secondary outcomeLeast squares mean· Randomization (Week 36), Week 88

Change From Randomization in Body Weight

GroupValue (kilogram (kg))Spread
Placebo11.90.43
Tirzepatide MTD-5.70.42
Secondary outcomeLeast squares mean· Randomization (Week 36), Week 88

Change From Randomization in Waist Circumference

GroupValue (centimetre (cm))Spread
Placebo8.30.44
Tirzepatide MTD-4.60.43
Secondary outcomeLeast squares mean· Randomization (Week 36), Week 88

Change From Randomization in Body Mass Index (BMI)

GroupValue (kilogram per square metre (kg/m^2))Spread
Placebo4.30.16
Tirzepatide MTD-2.10.15
Secondary outcomeLeast squares mean· Randomization (Week 36), Week 88

Change From Randomization in Fasting Glucose

GroupValue (milligrams per deciliter (mg/dL))Spread
Placebo7.740.548
Tirzepatide MTD-0.900.528
Secondary outcomeLeast squares mean· Randomization (Week 36), Week 88

Change From Randomization in Hemoglobin A1c (HbA1c)

GroupValue (percentage of HbA1c)Spread
Placebo0.250.017
Tirzepatide MTD-0.080.017
Secondary outcomeLeast squares mean· Randomization (Week 36), Week 88

Percent Change From Randomization in Fasting Insulin

GroupValue (percent change)Spread
Placebo23.34.37
Tirzepatide MTD-15.42.88

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Tirzepatide (lead-in)Participants received weekly doses of tirzepatide SC for 36 weeks, starting at 2.5 mg and increasing by 2.5 mg every 4 weeks, as tolerated, up to the MTD of either 10 mg or 15 mg.1 / 78216 / 782559 / 782
PlaceboParticipants received weekly doses of placebo SC for 52 weeks.1 / 33510 / 335100 / 335
Tirzepatide MTDParticipants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.1 / 33510 / 335124 / 335

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies8

Studies that cite this trial.

Studies with results

7 studies on this page

Indexing hint: Randomized controlled trial · 2026

6 results

People With Lowest Physical Functioning Scores Showed Greatest Improvement After Tirzepatide Treatment.

Li et al. 2026Obesity (Silver Spring, Md.)cited by 2

PMID 41187013PMC12724063DOI 10.1002/oby.70067PUB-41187013

CC BY6 results
Download PDFSee results (6)

Indexing hint: Randomized controlled trial · 2026

10 results

Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial.

Horn et al. 2026JAMA internal medicinecited by 32

PMID 41284285PMC12645400DOI 10.1001/jamainternmed.2025.6112PUB-41284285

Free to read · publisher termsCC BY-NC-ND10 results
Read at sourceSee results (10)

Indexing hint: Meta-analysis (pooled) · 2026

3 results

Weight Changes With Tirzepatide and Concomitant Weight-Inducing Medications: Post Hoc Analysis of Randomized Clinical Trials.

Galindo et al. 2026JAMA network open

PMID 41885866PMC13022736DOI 10.1001/jamanetworkopen.2026.3274PUB-41885866

Free to read · publisher termsCC BY-NC-ND3 results
Read at sourceSee results (3)

Indexing hint: Randomized controlled trial · 2025

6 results

Time to weight plateau with tirzepatide treatment in the SURMOUNT-1 and SURMOUNT-4 clinical trials.

Horn et al. 2025Clinical obesitycited by 12

PMID 39800653PMC12096058DOI 10.1111/cob.12734PUB-39800653

Free to read · publisher termsCC BY-NC-ND6 results
Read at sourceSee results (6)

Indexing hint: Randomized controlled trial · 2025

6 results

Early-Onset Obesity and Tirzepatide Treatment: A Post Hoc Analysis of the SURMOUNT Clinical Trials.

Gourgari et al. 2025Obesity (Silver Spring, Md.)cited by 4

PMID 40717199PMC12381612DOI 10.1002/oby.24348PUB-40717199

Free to read · publisher termsCC BY-NC-ND6 results
Read at sourceSee results (6)

Indexing hint: Randomized controlled trial · 2025

4 results

Tirzepatide Associated With Improved Health-Related Quality of Life in Adults With Obesity or Overweight in SURMOUNT-4.

Gibble et al. 2025Obesity (Silver Spring, Md.)cited by 4

PMID 40903801PMC12559773DOI 10.1002/oby.70011PUB-40903801

CC BY4 results
Download PDFSee results (4)

Indexing hint: Randomized controlled trial · 2024

5 results

Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.

Aronne et al. 2024JAMAcited by 689

PMID 38078870PMC10714284DOI 10.1001/jama.2023.24945PUB-38078870

Rights unknown5 results
Source linkSee results (5)

More studies

1 study on this page

PubMed tag: none · 2026

Nutritional status with tirzepatide in obesity: A post hoc analysis of the SURMOUNT-1-4 randomized clinical trials.

Almandoz et al. 2026Obesity pillarscited by 6

PMID 41640675PMC12865613DOI 10.1016/j.obpill.2026.100248PUB-41640675

Free to read · publisher termsCC BY-NC-ND
Read at source

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * 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 Exclusion Criteria: * 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

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