Completed

NCT Number: NCT04660643

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

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).

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Key information

Conditions

Obesity Body Weight Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases Overnutrition Overweight Pathological Conditions, Signs and Symptoms Prediabetic State Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

CEDIC, CABA, Buenos Aires, Argentina

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Tirzepatide

Drug

Administered SC

Other names: LY3298176

Placebo

Other

Administered SC

Primary outcomes

Percent Change From Randomization in Body Weight at Week 88

Time frame: 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 outcomes

Percent Change From Randomization in Body Weight at Week 64

Time frame: 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 Weight

Time frame: 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

Time frame: 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 Body Mass Index (BMI)

Time frame: 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 Fasting Glucose

Time frame: 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 Hemoglobin A1c (HbA1c)

Time frame: 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

Time frame: 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 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

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 Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)

Time frame: 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 Short Form 36 Version 2 Health Survey (SF 36v2) Acute Form - Physical Functioning Domain Score

Time frame: 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 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

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

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

Time frame: 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.
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

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 Baseline in BMI

Time frame: 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 Body Weight

Time frame: 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 Body Weight

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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 Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs)

Time frame: 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.
Change From Baseline in SBP, DBP

Time frame: 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 SF 36v2 Acute Form - Physical Functioning Domain Score

Time frame: 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.
Change From Baseline in IWQOL-Lite-CT - Physical Function Composite Score

Time frame: 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.

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study 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)

Acronym: SURMOUNT-4

Important dates

Study start: 2021
Primary completion: 2023
Study completion: 2023
First posted: Dec 9, 2020
Registry last updated: May 22, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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