A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight for the Maintenance of Weight Loss
- Registration Number
- NCT04660643
- Lead Sponsor
- Eli Lilly and Company
- Brief 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 783
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants received weekly doses of placebo SC for 52 weeks. Tirzepatide (lead-in) Tirzepatide 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. Tirzepatide MTD Tirzepatide Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks.
- Primary Outcome Measures
Name Time Method Percent Change From Randomization in Body Weight at Week 88 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.
- Secondary Outcome Measures
Name Time Method Change From Randomization in Hemoglobin A1c (HbA1c) Randomization (Week 36), Week 88 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.
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)) Randomization (Week 36), Week 88 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.
Percent Change From Baseline in Body Weight Baseline (Week 0), Week 88 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.
Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs) Baseline (Week 0), Week 88 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.
Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction From Baseline Baseline (Week 0) to Week 88 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.
Change From Baseline in Body Weight Baseline (Week 0), Week 88 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.
Change From Baseline in Waist Circumference Baseline (Week 0), Week 88 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.
Change From Baseline in Fasting Glucose Baseline (Week 0), Week 88 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.
Change From Baseline in HbA1c Baseline (Week 0), Week 88 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.
Percent Change From Baseline in Fasting Insulin Baseline (Week 0), Week 88 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.
Percent Change From Randomization in Body Weight at Week 64 Randomization (Week 36), 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.
Change From Randomization in Body Mass Index (BMI) Randomization (Week 36), Week 88 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.
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 Time to first occurrence of participants returning to \>95% baseline weight for those who lost ≥5% during the open-label lead-in period.
Change From Randomization in Body Weight Randomization (Week 36), Week 88 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.
Change From Randomization in Waist Circumference Randomization (Week 36), Week 88 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.
Change From Randomization in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) Randomization (Week 36), Week 88 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.
Change From Randomization in Impact of Weight on Quality of Life Lite Clinical Trials Version (IWQOL-Lite-CT) - Physical Function Composite Score Randomization (Week 36), Week 88 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.Percentage of Participants Who Maintain at Least 80% of the Body Weight Lost During the Open-Label Lead-In Period Week 88 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.
Change From Randomization in Fasting Glucose Randomization (Week 36), Week 88 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.
Percent Change From Randomization in Fasting Insulin Randomization (Week 36), Week 88 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.
Change From Randomization in Short Form 36 Version 2 Health Survey (SF 36v2) Acute Form - Physical Functioning Domain Score Randomization (Week 36), Week 88 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.Change From Baseline in BMI Baseline (Week 0), Week 88 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.
Change From Baseline in SBP, DBP Baseline (Week 0), Week 88 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.
Change From Baseline in IWQOL-Lite-CT - Physical Function Composite Score Baseline (Week 0), Week 88 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.Change From Baseline in SF 36v2 Acute Form - Physical Functioning Domain Score Baseline (Week 0), Week 88 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.
Trial Locations
- Locations (70)
North Texas Endocrine Center
🇺🇸Dallas, Texas, United States
Tribe Clinical Research, LLC
🇺🇸Greenville, South Carolina, United States
Glacier View Research Institute - Endocrinology
🇺🇸Kalispell, Montana, United States
Capital Area Research, LLC
🇺🇸Camp Hill, Pennsylvania, United States
Centro Médico Viamonte
🇦🇷Caba, Buenos Aires, Argentina
Asociación de Beneficencia Hospital Sirio Libanés
🇦🇷Buenos Aires, Argentina
Dallas Diabetes Research Center
🇺🇸Dallas, Texas, United States
Capital Clinical Research Center
🇺🇸Olympia, Washington, United States
CEDOES
🇧🇷Vitória, Espírito Santo, Brazil
Cline Research Center
🇧🇷Curitiba, Paraná, Brazil
China Medical University Hospital
🇨🇳Taichung, Taiwan
ISPEM - Instituto São José dos Campos em Pesquisas Médicas
🇧🇷São José dos Campos, São Paulo, Brazil
Centro de Endocrinologia Alcantara Gonzalez
🇵🇷Bayamon, Puerto Rico
Private Practice Dr. Martha Gomez Cuellar
🇵🇷San Juan, Puerto Rico
Aventiv Research Inc
🇺🇸Columbus, Ohio, United States
Biopharma Informatic, LLC
🇺🇸Houston, Texas, United States
University Clinical Investigators, Inc.
🇺🇸Tustin, California, United States
Care Partners Clinical Research
🇺🇸Jacksonville, Florida, United States
Endocrine Research Solutions, Inc.
🇺🇸Roswell, Georgia, United States
Rocky Mountain Clinical Research
🇺🇸Idaho Falls, Idaho, United States
Clinical Investigation Specialists
🇺🇸Gurnee, Illinois, United States
MedStar Health Research Institute (MedStar Physician Based Research Network)
🇺🇸Hyattsville, Maryland, United States
ActivMed Practices and Research
🇺🇸Methuen, Massachusetts, United States
Arcturus Healthcare , PLC, Troy Internal Medicine Research Division
🇺🇸Troy, Michigan, United States
Midwest Institute For Clinical Research
🇺🇸Indianapolis, Indiana, United States
Cotton O'Neil Clinic
🇺🇸Topeka, Kansas, United States
Núcleo de Pesquisa Clínica do Rio Grande do Sul
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Optumcare Colorado Springs - Monument
🇺🇸Monument, Colorado, United States
Lillestol Research
🇺🇸Fargo, North Dakota, United States
New West Physicians Clinical Research
🇺🇸Golden, Colorado, United States
Cahaba Research
🇺🇸Pelham, Alabama, United States
Scripps Memorial Hospital La Jolla
🇺🇸La Jolla, California, United States
National Research Institute - Wilshire
🇺🇸Los Angeles, California, United States
National Research Institute
🇺🇸Panorama City, California, United States
SKY Clinical Research Network Group-Blake
🇺🇸Union City, Georgia, United States
Healthcare Research Network - Chicago
🇺🇸Flossmoor, Illinois, United States
American Health Network of Indiana, LLC - New Albany
🇺🇸New Albany, Indiana, United States
StudyMetrix Research
🇺🇸Saint Peters, Missouri, United States
PharmQuest
🇺🇸Greensboro, North Carolina, United States
Intend Research, LLC
🇺🇸Norman, Oklahoma, United States
The University of Texas Health Science Center at Houston
🇺🇸Bellaire, Texas, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Northwest Houston Heart Center
🇺🇸Tomball, Texas, United States
North Hills Family Medicine/North Hills Medical Research
🇺🇸North Richland Hills, Texas, United States
Health Research of Hampton Roads, Inc.
🇺🇸Newport News, Virginia, 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
L-MARC Research Center
🇺🇸Louisville, Kentucky, United States
University of North Carolina Medical Center
🇺🇸Chapel Hill, North Carolina, United States
Wake Forest University Baptist Medical Center (WFUBMC)
🇺🇸Winston-Salem, North Carolina, United States
Centro de Pesquisa Sao Lucas
🇧🇷Campinas, São Paulo, Brazil
Mautalen Salud e Investigación
🇦🇷Buenos Aires, Ciudad Autónoma De Buenos Aire, Argentina
CPQuali Pesquisa Clínica
🇧🇷São Paulo, Brazil
Summit Research Network
🇺🇸Portland, Oregon, United States
Chung Shan Medical University Hospital
🇨🇳Taichung, Taiwan
National Cheng-Kung Uni. Hosp.
🇨🇳Tainan, Taiwan
Renstar Medical Research
🇺🇸Ocala, Florida, United States
South Florida Clinical Research Institute
🇺🇸Margate, Florida, United States
Centennial Medical Group
🇺🇸Elkridge, Maryland, United States
BR Trials - Ensaios Clinicos e Consultoria
🇧🇷Sao Paulo, São Paulo, Brazil
Wellness clinical Research Vega Baja
🇵🇷Vega Baja, Puerto Rico
Instituto Médico Catamarca IMEC
🇦🇷Rosario, Santa Fe, Argentina
IBPClin - Instituto Brasil de Pesquisa Clínica
🇧🇷Rio de Janeiro, Brazil
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
CEDIC
🇦🇷Caba, Buenos Aires, Argentina
Stat Research S.A.
🇦🇷Ciudad Autónoma de Buenos Aire, Buenos Aires, Argentina
Centro Medico Dr Laura Maffei Investigacion Clinica Aplicada
🇦🇷Ciudad Autonoma de Buenos Aire, Ciudad Autónoma De Buenos Aire, Argentina
East-West Medical Research Institute
🇺🇸Honolulu, Hawaii, United States
Rainier Clinical Research Center
🇺🇸Renton, Washington, United States