A Study of LY3502970 in Participants With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the efficacy and safety of LY3502970 in participants with type 2 diabetes (T2D) who failed to achieve adequate glycemic control on diet and exercise alone or on a stable dose of metformin. This study will last about 30 weeks.

Official Title
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A Phase 2 Study of Once-Daily LY3502970 Compared With Placebo and Once-Weekly Dulaglutide in Participants With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: LY3502970
* Drug: Dulaglutide
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have been diagnosed with Type 2 Diabetes on diet and exercise and/or a stable dose of metformin Have a stable body weight for the 3 months prior to randomization Have a body mass index (BMI) ≥23 kilogram/square meter (kg/m²) Males must agree to use highly effective methods of contraception Women not of childbearing potential (WNOCBP) may participate in this trial Note: Hormone replacement therapy in post-menopausal women is allowed but women must be on stable therapy for 3 months prior to day 1. Exclusion Criteria: Have Type 1 diabetes mellitus (T1DM) or history of ketoacidosis or hyperosmolar coma Have a history of diabetic retinopathy, diabetic maculopathy, or severe non-proliferative diabetic retinopathy that requires immediate treatment intervention Have had more than 1 episode of severe hypoglycemia and aware of hypoglycemic symptoms Have acute or chronic pancreatitis Have obesity induced other endocrine disorders (Cushing's syndrome or Prader - Willi syndrome) Have gastric emptying abnormality or chronically take medications impacting GI motility Have poorly controlled hypertension Have the following heart conditions within the last 6 months: myocardial infarction (MI), unstable angina, coronary artery bypass graft, percutaneous coronary intervention (diagnostic angiograms are permitted), transient ischemic attack (TIA), cerebrovascular accident (stroke)or decompensated congestive heart failure, or IV heart failure Have any symptoms of other liver diseases besides nonalcoholic fatty liver disease (NAFLD) Have HIV, or Hepatitis B or Hepatitis C

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: 3 milligrams (mg) LY3502970<br>Participants received maintenance dose of 3 mg with dose escalation starting from 2 mg LY3502970 administered orally once daily (QD). | Drug: LY3502970<br>* Administered orally<br>|
| Experimental: 12 mg LY3502970<br>Participants received maintenance dose 12 mg with dose escalation starting from 2 mg, 6 mg and then 12 mg LY3502970 administered orally QD. | Drug: LY3502970<br>* Administered orally<br>|
| Experimental: 24 mg LY3502970<br>Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally QD. | Drug: LY3502970<br>* Administered orally<br>|
| Experimental: 36 mg LY3502970 - 1<br>Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 administered orally QD. | Drug: LY3502970<br>* Administered orally<br>|
| Experimental: 36 mg LY3502970 - 2<br>Participants received maintenance dose 36 mg with dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 administered orally QD. | Drug: LY3502970<br>* Administered orally<br>|
| Experimental: 45 mg LY3502970 - 1<br>Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally QD. | Drug: LY3502970<br>* Administered orally<br>|
| Experimental: 45 mg LY3502970 - 2<br>Participants received maintenance dose 45 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally QD. | Drug: LY3502970<br>* Administered orally<br>|
| Active Comparator: 1.5 mg Dulaglutide<br>Participants received 1.5 mg Dulaglutide administered subcutaneously (SC) once weekly (QW). | Drug: Dulaglutide<br>* Administered subcutaneously<br>|
| Placebo Comparator: Placebo<br>Participants received matching placebo. | Drug: Placebo<br>* Administered orally<br>Drug: Placebo<br>* Administered subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c in LY3502970 as Compared to Placebo | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed model repeated measures (MMRM) model with Baseline + Country + Baseline HbA1c Group (<=8.0%, >8.0%) + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c in LY3502970 as Compared to Dulaglutide | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed model repeated measures (MMRM) model with Baseline + Country + Baseline HbA1c Group (<=8.0%, >8.0%) + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. | Baseline, Week 26 | 
| Percentage of Participants With HbA1c ≤ 6.5% | Percentage of Participants with HbA1c ≤ 6.5%. Odds ratio was calculated using logistic regression model. | Week 26 | 
| Percentage of Participants With HbA1c <7.0% | Percentage of Participants with HbA1c <7.0%. Odds ratio was calculated using logistic regression model. | Week 26 | 
| Change From Baseline in Fasting Serum Glucose | Fasting glucose is a test to determine sugar levels in blood sample after an overnight fast. LS mean was determined by MMRM model with Baseline + Country + Baseline HbA1c Group (<=8.0%, 8.0%) + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. | Baseline, Week 26 | 
| Change From Baseline in Body Weight | LS mean was determined by MMRM model with Baseline + Country + Baseline HbA1c Group (<=8.0%, >8.0%) + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. | Baseline, Week 26 | 
| Pharmacokinetics (PK): Steady State Area Under the Concentration Curve (AUC) of LY3502970 | PK: Steady State AUC of LY3502970 | Pre-dose (Week (wk) 0, wk 8, wk 12, and wk 26); Post-dose (wk 4, wk 8, wk 16, wk 20, and end of treatment). |