A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight for the Maintenance of Weight Loss (SURMOUNT-4)

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).

Study Overview

• Status: Completed
• Conditions: Obesity; Overweight
• Intervention / Treatment: Drug: Tirzepatide; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 783
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1419AHN
    • Asociación de Beneficencia Hospital Sirio Libanés
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1120AAC
      • Centro Medico Viamonte
    • Caba, Buenos Aires, Argentina, C1060ABN
      • CEDIC
    • Ciudad Autónoma de Buenos Aire, Buenos Aires, Argentina, C1023AAB
      • STAT Research S.A.
  • Ciudad Autónoma De Buenos Aire
    • Buenos Aires, Ciudad Autónoma De Buenos Aire, Argentina, C1128AAF
      • Mautalen Salud e Investigación
    • Ciudad Autonoma de Buenos Aire, Ciudad Autónoma De Buenos Aire, Argentina, C1425AGC
      • Centro Medico Dr Laura Maffei Investigacion Clinica Aplicada
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • Instituto Médico Catamarca IMEC
• Brazil
  • Rio de Janeiro, Brazil, 22241-180
    • IBPClin - Instituto Brasil de Pesquisa Clínica
  • São Paulo, Brazil, 01228-000
    • CPQuali Pesquisa Clínica
  • Espírito Santo
    • Vitória, Espírito Santo, Brazil, 29055450
      • CEDOES
  • Paraná
    • Curitiba, Paraná, Brazil, 80030-480
      • Cline Research Center
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90430-001
      • Nucleo de Pesquisa Clínica do Rio Grande do Sul
  • São Paulo
    • Campinas, São Paulo, Brazil, 13034-685
      • Centro de Pesquisa São Lucas
    • Sao Paulo, São Paulo, Brazil, 03325-050
      • BR Trials - Ensaios Clinicos e Consultoria
    • São José dos Campos, São Paulo, Brazil, 12243-280
      • ISPEM - Instituto São Jose dos Campos em Pesquisas Medicas
• Puerto Rico
  • Bayamon, Puerto Rico, 00959
    • Centro de Endocrinologia Alcantara Gonzalez
  • San Juan, Puerto Rico, 00921
    • Private Practice Dr. Martha Gomez Cuellar
  • Vega Baja, Puerto Rico, 00694
    • Wellness clinical Research Vega Baja
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taichung, Taiwan, 402
    • Chung Shan Medical University Hospital
  • Tainan, Taiwan, 704
    • National Cheng-Kung Uni. Hosp.
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
• United States
  • Alabama
    • Pelham, Alabama, United States, 35124
      • Cahaba Research
  • California
    • La Jolla, California, United States, 92037
      • Scripps Memorial Hospital La Jolla
    • Los Angeles, California, United States, 90057
      • National Research Institute - Wilshire
    • Panorama City, California, United States, 91402
      • National Research Institute
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
    • Tustin, California, United States, 92780
      • University Clinical Investigators, Inc.
  • Colorado
    • Golden, Colorado, United States, 80401
      • New West Physicians Clinical Research
    • Monument, Colorado, United States, 80132
      • Optumcare Colorado Springs - Monument
  • Florida
    • Jacksonville, Florida, United States, 32277
      • Care Partners Clinical Research
    • Margate, Florida, United States, 33063
      • South Florida Clinical Research Institute
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Tampa, Florida, United States, 33613
      • ForCare Clinical Research
  • Georgia
    • Roswell, Georgia, United States, 30076
      • Endocrine Research Solutions, Inc.
    • Union City, Georgia, United States, 30291
      • SKY Clinical Research Network Group-Blake
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Rocky Mountain Clinical Research
  • Illinois
    • Flossmoor, Illinois, United States, 60422
      • Healthcare Research Network - Chicago
    • Gurnee, Illinois, United States, 60031
      • Clinical Investigation Specialists
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Midwest Institute for Clinical Research
    • New Albany, Indiana, United States, 47150
      • American Health Network of Indiana, LLC - New Albany
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Clinic
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • L-MARC Research Center
  • Maryland
    • Elkridge, Maryland, United States, 21075
      • Centennial Medical Group
    • Hyattsville, Maryland, United States, 20782
      • MedStar Health Research Institute (MedStar Physician Based Research Network)
  • Massachusetts
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Practices and Research
  • Michigan
    • Troy, Michigan, United States, 48098
      • Arcturus Healthcare , PLC, Troy Internal Medicine Research Division
  • Missouri
    • Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research
  • Montana
    • Kalispell, Montana, United States, 59901
      • Glacier View Research Institute - Endocrinology
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina Medical Center
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Baptist Medical Center (WFUBMC)
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Lillestol Research
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Aventiv Research Inc
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Intend Research, LLC
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • Capital Area Research, LLC
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Tribe Clinical Research, LLC
  • Texas
    • Bellaire, Texas, United States, 77401
      • The University of Texas Health Science Center at Houston
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes Research Center
    • Dallas, Texas, United States, 75231
      • North Texas Endocrine Center
    • Houston, Texas, United States, 77043
      • Biopharma Informatic, LLC
    • North Richland Hills, Texas, United States, 76180
      • North Hills Family Medicine/North Hills Medical Research
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.
    • Tomball, Texas, United States, 77375
      • Northwest Houston Heart Center
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads, Inc.
  • Washington
    • Olympia, Washington, United States, 98502
      • Capital Clinical Research Center
    • Renton, Washington, United States, 98057
      • Rainier Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Experimental: Tirzepatide MTD; Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Placebo Comparator: Placebo; Participants received weekly doses of placebo SC for 52 weeks.	Other: Placebo; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	Baseline (Week 0), Week 88

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: 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

Publications and helpful links

Helpful Links

• A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight for the Maintenance of Weight Loss (SURMOUNT-4)

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2021
• Primary Completion (Actual): April 25, 2023
• Study Completion (Actual): May 18, 2023

Study Registration Dates

• First Submitted: December 1, 2020
• First Submitted That Met QC Criteria: December 8, 2020
• First Posted (Actual): December 9, 2020

Study Record Updates

• Last Update Posted (Actual): May 22, 2024
• Last Update Submitted That Met QC Criteria: May 21, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Prediabetes; Metabolism and Nutrition Disorder
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Body Weight; Body Weight Changes; Obesity; Weight Loss; Overweight; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Tirzepatide
• Other Study ID Numbers: 17247; I8F-MC-GPHN (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing 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.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No