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

Obesity Clinical Trial

— SURMOUNT-4  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04660643
• Other study ID #: 17247
• Secondary ID: I8F-MC-GPHN
• Status: Completed
• Phase: Phase 3
• Start date: March 29, 2021
• Est. completion date: May 18, 2023

Study information

• Verified date: May 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 or switched to placebo. The study lasted about 2 years (25 visits).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 783
• Est. completion date: May 18, 2023
• Est. primary completion date: April 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Obesity
• Overweight
• Weight Loss

Intervention

Drug:
• Tirzepatide
Administered SC

Other:
• Placebo
Administered SC

Locations

Country	Name	City	State
Argentina	Asociación de Beneficencia Hospital Sirio Libanés	Buenos Aires
Argentina	Mautalen Salud e Investigación	Buenos Aires	Ciudad Autónoma De Buenos Aire
Argentina	CEDIC	Caba	Buenos Aires
Argentina	Centro Médico Viamonte	Caba	Buenos Aires
Argentina	Centro Medico Dr Laura Maffei Investigacion Clinica Aplicada	Ciudad Autonoma de Buenos Aire	Ciudad Autónoma De Buenos Aire
Argentina	Stat Research S.A.	Ciudad Autónoma de Buenos Aire	Buenos Aires
Argentina	Instituto Médico Catamarca IMEC	Rosario	Santa Fe
Brazil	Centro de Pesquisa Sao Lucas	Campinas	São Paulo
Brazil	Cline Research Center	Curitiba	Paraná
Brazil	Núcleo de Pesquisa Clínica do Rio Grande do Sul	Porto Alegre	Rio Grande Do Sul
Brazil	IBPClin - Instituto Brasil de Pesquisa Clínica	Rio de Janeiro
Brazil	ISPEM - Instituto São José dos Campos em Pesquisas Médicas	São José dos Campos	São Paulo
Brazil	BR Trials - Ensaios Clinicos e Consultoria	Sao Paulo	São Paulo
Brazil	CPQuali Pesquisa Clínica	São Paulo
Brazil	CEDOES	Vitória	Espírito Santo
Puerto Rico	Centro de Endocrinologia Alcantara Gonzalez	Bayamon
Puerto Rico	Private Practice Dr. Martha Gomez Cuellar	San Juan
Puerto Rico	Wellness clinical Research Vega Baja	Vega Baja
Taiwan	China Medical University Hospital	Taichung
Taiwan	Chung Shan Medical University Hospital	Taichung
Taiwan	National Cheng-Kung Uni. Hosp.	Tainan
Taiwan	National Taiwan University Hospital	Taipei
United States	The University of Texas Health Science Center at Houston	Bellaire	Texas
United States	Capital Area Research, LLC	Camp Hill	Pennsylvania
United States	University of North Carolina Medical Center	Chapel Hill	North Carolina
United States	Aventiv Research Inc	Columbus	Ohio
United States	Dallas Diabetes Research Center	Dallas	Texas
United States	North Texas Endocrine Center	Dallas	Texas
United States	Centennial Medical Group	Elkridge	Maryland
United States	Lillestol Research	Fargo	North Dakota
United States	Healthcare Research Network - Chicago	Flossmoor	Illinois
United States	New West Physicians Clinical Research	Golden	Colorado
United States	PharmQuest	Greensboro	North Carolina
United States	Tribe Clinical Research, LLC	Greenville	South Carolina
United States	Clinical Investigation Specialists	Gurnee	Illinois
United States	East-West Medical Research Institute	Honolulu	Hawaii
United States	Biopharma Informatic, LLC	Houston	Texas
United States	MedStar Health Research Institute (MedStar Physician Based Research Network)	Hyattsville	Maryland
United States	Rocky Mountain Clinical Research	Idaho Falls	Idaho
United States	Midwest Institute For Clinical Research	Indianapolis	Indiana
United States	Care Partners Clinical Research	Jacksonville	Florida
United States	Glacier View Research Institute - Endocrinology	Kalispell	Montana
United States	Scripps Memorial Hospital La Jolla	La Jolla	California
United States	National Research Institute - Wilshire	Los Angeles	California
United States	L-MARC Research Center	Louisville	Kentucky
United States	South Florida Clinical Research Institute	Margate	Florida
United States	ActivMed Practices and Research	Methuen	Massachusetts
United States	Optumcare Colorado Springs - Monument	Monument	Colorado
United States	American Health Network of Indiana, LLC - New Albany	New Albany	Indiana
United States	Weill Cornell Medical College	New York	New York
United States	Health Research of Hampton Roads, Inc.	Newport News	Virginia
United States	Intend Research, LLC	Norman	Oklahoma
United States	North Hills Family Medicine/North Hills Medical Research	North Richland Hills	Texas
United States	Renstar Medical Research	Ocala	Florida
United States	Capital Clinical Research Center	Olympia	Washington
United States	National Research Institute	Panorama City	California
United States	Cahaba Research	Pelham	Alabama
United States	Summit Research Network	Portland	Oregon
United States	Rainier Clinical Research Center	Renton	Washington
United States	Endocrine Research Solutions, Inc.	Roswell	Georgia
United States	StudyMetrix Research	Saint Peters	Missouri
United States	Clinical Trials of Texas, Inc.	San Antonio	Texas
United States	Artemis Institute for Clinical Research	San Diego	California
United States	ForCare Clinical Research	Tampa	Florida
United States	Northwest Houston Heart Center	Tomball	Texas
United States	Cotton O'Neil Clinic	Topeka	Kansas
United States	Arcturus Healthcare , PLC, Troy Internal Medicine Research Division	Troy	Michigan
United States	University Clinical Investigators, Inc.	Tustin	California
United States	SKY Clinical Research Network Group-Blake	Union City	Georgia
United States	Wake Forest University Baptist Medical Center (WFUBMC)	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Puerto Rico,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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