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

Study Overview
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Brief Summary
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This is a study of tirzepatide in participants with obesity or overweight. The main purpose is to learn more about how tirzepatide maintains body weight loss. The study has two phases: a lead-in phase in which all participants take tirzepatide and a treatment phase in which participants will either continue tirzepatide or switch to placebo. The study will last about 2 years (25 visits).

Official Title
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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)

Conditions
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Obesity, Overweight

Intervention / Treatment
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* Drug: Tirzepatide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tirzepatide<br>Tirzepatide administered subcutaneously (SC) | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Placebo Comparator: Placebo<br>Placebo administered SC | Other: Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Randomization (Week 36) in Body Weight | Percent change from randomization in body weight | Randomization, Week 88 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Randomization in Body Weight | Change from randomization in body weight | Randomization, Week 88 | 
| Change from Randomization in Waist Circumference | Change from randomization in waist circumference | Randomization, Week 88 | 
| Percentage of Participants Who Maintain ≥80% of the Body Weight Lost During the Open-Label Period | Percentage of participants who maintain ≥80% of the body weight lost during the open-label period | Week 88 | 
| Percentage of Participants Who Achieve ≥5% Body Weight Reduction | Percentage of participants who achieve ≥5% body weight reduction | Week 88 | 
| Percentage of Participants Who Achieve ≥10% Body Weight Reduction | Percentage of participants who achieve ≥10% body weight reduction | Week 88 | 
| Time to First Occurrence of Participants Returning to >95% Baseline Weight for Those Who Lost ≥5% during the Open-Label Period | Time to first occurrence of participants returning to >95% baseline weight for those who lost ≥5% during the open-label period | Randomization, Week 88 | 
| Percent Change from Randomization in Body Weight | Percent change from randomization in body weight | Randomization, Week 64 | 
| Change from Randomization in Body Mass Index (BMI) | Change from randomization in BMI | Randomization, Week 88 | 
| Change from Randomization in Fasting Glucose | Change from randomization in fasting glucose | Randomization, Week 88 | 
| Change from Randomization in Hemoglobin A1c (HbA1c) | Change from randomization in HbA1c | Randomization, Week 88 | 
| Change from Randomization in Fasting Insulin | Change from randomization in fasting insulin | Randomization, Week 88 | 
| Change from Randomization in Total Cholesterol | Change from randomization in total cholesterol | Randomization, Week 88 | 
| Change from Randomization in Low Density Lipoprotein (LDL) Cholesterol | Change from randomization in LDL cholesterol | Randomization, Week 88 | 
| Change from Randomization in High Density Lipoprotein (HDL) Cholesterol | Change from randomization in HDL cholesterol | Randomization, Week 88 | 
| Change from Randomization in Very Low Density Lipoprotein (VLDL) Cholesterol | Change from randomization in VLDL cholesterol | Randomization, Week 88 | 
| Change from Randomization in Triglycerides | Change from randomization in triglycerides | Randomization, Week 88 | 
| Change from Randomization in Free Fatty Acids | Change from randomization in free fatty acids | Randomization, Week 88 | 
| Change from Randomization in Systolic Blood Pressure (SBP) | Change from randomization in SBP | Randomization, Week 88 | 
| Change from Randomization in Diastolic Blood Pressure (DBP) | Change from randomization in DBP | Randomization, 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, 1-week recall assesses participants' health-related quality of life (HRQoL) on 8 domains; 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning 7) limitations in usual role due to emotional problems; and 8) general mental health. Domain scores are norm-based and presented in the form of T-scores, with a mean of 50 and standard deviation of 10, with higher scores indicating better levels of function and/or better health. | Randomization, 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. Individual composite scale scores and a total score can be computed and are presented on a scale of 0 to 100, with higher scores indicating better function. | Randomization, Week 88 | 
| Change from Baseline in Body Weight | Change from baseline in body weight | Baseline, Week 88 | 
| Percent Change from Baseline in Body Weight | Percent change from baseline in body weight | Baseline, Week 88 | 
| Change from Baseline in BMI | Change from baseline in BMI | Baseline, Week 88 | 
| Percentage of Participants Who Achieve ≥15% Body Weight Reduction | Percentage of participants who achieve ≥15% body weight reduction | Week 88 | 
| Change from Baseline in Waist Circumference | Change from baseline in waist circumference | Baseline, Week 88 | 
| Change from Baseline in Fasting Glucose | Change from baseline in fasting glucose | Baseline, Week 88 | 
| Change from Baseline in HbA1c | Change from baseline in HbA1c | Baseline, Week 88 | 
| Change from Baseline in Fasting Insulin | Change from baseline in fasting insulin | Baseline, Week 88 | 
| Change from Baseline in Total Cholesterol | Change from baseline in total cholesterol | Baseline, Week 88 | 
| Change from Baseline in HDL Cholesterol | Change from baseline in HDL cholesterol | Baseline, Week 88 | 
| Change from Baseline in LDL Cholesterol | Change from baseline in LDL cholesterol | Baseline, Week 88 | 
| Change from Baseline in VLDL Cholesterol | Change from baseline in VLDL cholesterol | Baseline, Week 88 | 
| Change from Baseline in Triglycerides | Change from baseline in triglycerides | Baseline, Week 88 | 
| Change from Baseline in Free Fatty Acids | Change from baseline in free fatty acids | Baseline, Week 88 | 
| Change from Baseline in SBP | Change from baseline in SBP | Baseline, Week 88 | 
| Change from Baseline in DBP | Change from baseline in DBP | Baseline, Week 88 | 
| Change from Randomization in SF 36v2 Acute Form Physical Functioning Domain Score | The SF-36v2 acute form, 1-week recall assesses participants' HRQoL on 8 domains; 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning 7) limitations in usual role due to emotional problems; and 8) general mental health. Domain scores are norm-based and presented in the form of T-scores, with a mean of 50 and standard deviation of 10, with higher scores indicating better levels of function and/or better health. | Baseline, 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. Individual composite scale scores and a total score can be computed and are presented on a scale of 0 to 100, with higher scores indicating better function. | Baseline, Week 88 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metabolism and Nutrition Disorder, Prediabetes