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

Phase 3

Completed

Conditions: Overweight
Obesity

Interventions: Other: Placebo
Drug: Tirzepatide

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

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 & 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): 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
Artemis Institute for Clinical Research
🇺🇸
San Diego, California, United States
University Clinical Investigators, Inc.
🇺🇸
Tustin, California, United States
New West Physicians Clinical Research
🇺🇸
Golden, Colorado, United States
Optumcare Colorado Springs - Monument
🇺🇸
Monument, Colorado, United States
Care Partners Clinical Research
🇺🇸
Jacksonville, Florida, United States
South Florida Clinical Research Institute
🇺🇸
Margate, Florida, United States
Scroll for more (60 remaining)
Cahaba Research
🇺🇸Pelham, Alabama, United States