A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Who Have Obesity or Are Overweight

Study Overview
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Brief Summary
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This is a study of tirzepatide in participants with type 2 diabetes who have obesity or are overweight. The main purpose is to learn more about how tirzepatide affects body weight. The study will last 79 weeks (22 visits).

Official Title
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Efficacy and Safety of Tirzepatide Once Weekly in Participants With Type 2 Diabetes Who Have Obesity or Are Overweight: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-2)

Conditions
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Type 2 Diabetes, Overweight, Obesity

Intervention / Treatment
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* Drug: Tirzepatide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have Type 2 Diabetes (T2DM) with HbA1c ≥7% to ≤10% at screening, on stable therapy for the last 3 months prior to screening. T2DM may be treated with diet/exercise alone or any oral glycemic-lowering agent (as per local labeling) EXCEPT dipeptidyl peptidase 4 (DPP-4) inhibitors or glucagon like peptide-1 receptor agonists (GLP-1 RAs) Have a BMI of ≥27 kg/m² Are overweight or have obesity Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight Are at least 18 years of age and age of majority per local laws and regulations Exclusion Criteria: Have Type 1 diabetes mellitus, history of ketoacidosis or hyperosmolar state/coma or any other types of diabetes except T2DM Have at least 2 confirmed fasting self-monitoring blood glucose (SMBG) values >270 mg/dL(on 2 nonconsecutive days) prior to Visit 3 Have proliferative diabetic retinopathy OR diabetic macular edema OR non-proliferative diabetic retinopathy that requires acute treatment Have self-reported change in body weight >5kg within 3 months prior to screening Have had a history of chronic or acute pancreatitis 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 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: 10 mg Tirzepatide<br>10 mg Tirzepatide administered subcutaneously (SC) | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Experimental: 15 mg Tirzepatide<br>15 mg Tirzepatide administered 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 in Body Weight | Percent Change from randomization in body weight | Randomization, 72 Weeks | 
| Percentage of Participants Who Achieve ≥5% Body Weight Reduction from Randomization | Percentage of participants who achieve ≥5% body weight reduction from randomization | 72 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieve ≥10% Body Weight Reduction from Randomization | Percentage of participants who achieve ≥10% body weight reduction from randomization | 72 Weeks | 
| Percentage of Participants Who Achieve ≥15% Body Weight Reduction from Baseline | Percentage of participants who achieve ≥15% body weight reduction from randomization | 72 Weeks | 
| Change from Randomization in Absolute Body Weight | Change from randomization in absolute body weight | Randomization, 72 Weeks | 
| Change from Randomization in Body Mass Index (BMI) | Change from randomization in BMI | Randomization, 72 Weeks | 
| Change from Randomization in HbA1c | Change from randomization in HbA1c | Randomization, 72 Weeks | 
| Percentage of Participants who Achieve HbA1c <7% | Percentage of Participants who Achieve HbA1c <7% | 72 Weeks | 
| Percentage of Participants Who Achieve HbA1c ≤6.5% | Percentage of participants who achieve HbA1c ≤6.5% | 72 Weeks | 
| Percentage of Participants Who Achieve HbA1c <5.7% | Percentage of participants who achieve HbA1c <5.7% | 72 Weeks | 
| Change from Randomization in Fasting Glucose | Change from randomization in fasting glucose | Randomization, 72 Weeks | 
| Change from Randomization in Waist Circumference | Change from randomization in waist circumference | Randomization, 72 Weeks | 
| Change from Randomization in Total Cholesterol | Change from randomization in total cholesterol | Randomization, 72 Weeks | 
| Change from Randomization in Low Density Lipid (LDL)-Cholesterol | Change from randomization in LDL-cholesterol | Randomization, 72 Weeks | 
| Change from Randomization in High Density Lipid (HDL) Cholesterol | Change from randomization in HDL cholesterol | Randomization, 72 Weeks | 
| Change from Randomization in Very Low Density Lipid (VLDL) Cholesterol | Change from randomization in VLDL cholesterol | Randomization, 72 Weeks | 
| Change from Randomization in Triglycerides | Change from randomization in triglycerides | Randomization, 72 Weeks | 
| Change from Randomization in Free Fatty Acids | Change from randomization in free fatty acids | Randomization, 72 Weeks | 
| Change from Randomization in Systolic Blood Pressure (SBP) | Change from randomization in SBP | Randomization, 72 Weeks | 
| Change from Randomization in Diastolic Blood Pressure (DBP) | Change from randomization in DBP | Randomization, 72 Weeks | 
| Change from Randomization in Fasting Insulin | Change from randomization in fasting insulin | Randomization, 72 Weeks | 
| Change from Randomization in Short Form 36 Health Survey version 2 (SF-36v2) acute form Physical Functioning domain score | The Short Form 36 Version 2 (SF-36v2 ) acute form, 1-week recall, assesses participants' health-related quality of life (HRQoL) on 8 domains: 1) limitations in physical functioning; 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, 72 Weeks | 
| 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, 72 Weeks | 
| Pharmacokinetics (PK): Steady State Area Under the Concentration Curve (AUC) of Tirzepatide | PK: Steady State AUC of Tirzepatide | Baseline through Week 72 | 

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