A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy of tirzepatide in participants with type 2 diabetes.

Official Title
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A Phase 2, Double-Blind, Placebo-Controlled, 3-Month Trial of LY3298176 Versus Placebo in Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Tirzepatide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have type 2 diabetes (T2DM) for ≥6 months according to the Criteria for Diagnosing Type 2 Diabetes Mellitus (American Diabetes Association 2017). Have HbA1c of 7.0% to 10.5%, inclusive, as assessed by the central laboratory. If on metformin, have been treated with stable doses of metformin for at least 3 months. Have a body mass index (BMI) between 23 and 45 (Inclusive) kilograms per square meter. Exclusion Criteria: Have type 1 diabetes (T1D). Have used any glucose-lowering medication other than metformin within 3 months prior to study entry or during screening/lead-in period or have used any glucagon-like peptide-1 receptor agonists (GLP-1 RAs) at any time in the past 12 months. Have had any of the following cardiovascular conditions: acute myocardial infarction (MI), New York Heart Association Class III or Class IV heart failure, or cerebrovascular accident (stroke). Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine aminotransferase (ALT) level >2.5 times the upper limit of the reference range, as determined by the central laboratory at study entry; participants with NAFLD are eligible for participation in this trial. Have had chronic or acute pancreatitis any time prior to study entry. Have an estimated glomerular filtration rate (eGFR) <45 milliliters/minute/1.73 square meter, calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation. Have serum calcitonin ≥20 picograms per milliliter, as determined by the central laboratory at study entry. Have any condition that is a contraindication for use of the GLP-1 RA class (per country-specific labels) at study entry or develop such condition between study entry and randomization.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: 4,8,12mg Tirzepatide<br>Participants received Tirzepatide by subcutaneous (SC) injection in three dose escalations starting with 4 milligrams (mg) for four weeks followed by 8mg for four weeks followed by 12mg for four weeks. | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Experimental: 2.5,5,10,15mg Tirzepatide<br>Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks. | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Experimental: 2.5,7.5,15mg Tirzepatide<br>Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks. | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Placebo Comparator: Placebo<br>Placebo administered by SC injection. | Drug: Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Haemoglobin A1c (HbA1c) | Least squares (LS) mean was calculated using mixed model repeated measures model (MMRM) with baseline + baseline BMI group + baseline metformin flag + treatment + time + treatment*time as fixed factors. | Baseline, 3 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving HbA1c Target of <7.0% | Percentage of participants achieving HbA1c target of < (less than) 7.0%. | 3 Months | 
| Change From Baseline in Fasting Blood Glucose (FBG) | LSMean was calculated using MMRM model with baseline + baseline HbA1C group + baseline BMI group + baseline Metformin flag + treatment + time + treatment*time as fixed factors. | Baseline, 3 Months | 
| Change From Baseline in Body Weight | LSMean was calculated using MMRM model with baseline + baseline HbA1C group + baseline BMI group + baseline Metformin flag + treatment + time + treatment*time as fixed factors. | Baseline, 3 Months | 
| Change From Baseline in Waist Circumference | LSMean was calculated using MMRM model with baseline + baseline HbA1C group + baseline BMI group + baseline Metformin flag + treatment + time + treatment*time as fixed factors. | Baseline, 3 Months | 
| Number of Participants With Anti Drug Antibodies | Number of participants with anti drug antibodies. | Baseline through 3 Months | 
| Number of Episodes of Total Hypoglycemia Episodes | Number of episodes of total hypoglycemia episodes with plasma glucose <= ( less than or equal to) 54 mg/dL. | Baseline through 3 Months | 
| Pharmacokinetics (PK): Average Trough Concentration (Conctrough) of Tirzepatide | Pharmacokinetics (PK): Average Trough Concentration (Conctrough) of Tirzepatide. | Week 4, 8 12: Pre-dose |