A Study of Orforglipron (LY3502970) in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone

Study Overview
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Brief Summary
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The main purpose of this study is to determine safety and efficacy of orforglipron compared with placebo in adult participants with type 2 diabetes and inadequate glycemic control with diet and exercise alone. The study will last approximately 54 weeks.

Official Title
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A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once Daily Oral LY3502970 Compared With Placebo in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Orforglipron
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have Type 2 Diabetes Have HbA1c ≥7.0% (53 mmol/mol) to ≤9.5% (80 mmol/mol) despite diet and exercise treatment, as determined by the central laboratory at screening. Are naïve to insulin therapy except for gestational diabetes or ≤14 days use for acute treatment and have not used any oral or injectable antihyperglycemic medications during the 90 days preceding screening or between screening and randomization. Are of stable weight (±5%) for at least 90 days prior to screening and agree to not initiate an intensive diet or exercise program during the study with the intent of reducing body weight other than the lifestyle and/or dietary measures for diabetes treatment. Have a body mass index (BMI) ≥23.0 kilogram/square meter (kg/m²) at screening. Exclusion Criteria: Have Type 1 Diabetes Have a history of ketoacidosis or hyperosmolar state or coma within the last 6 months prior to screening, or between screening and randomization. Currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema Have New York Heart Association functional classification IV congestive heart failure. Have acute or chronic pancreatitis

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: Orforglipron Dose 1<br>Participants will receive orforglipron orally. | Drug: Orforglipron<br>* Administered orally.<br>* Other names: LY3502970;|
| Experimental: Orforglipron Dose 2<br>Participants will receive orforglipron orally. | Drug: Orforglipron<br>* Administered orally.<br>* Other names: LY3502970;|
| Experimental: Orforglipron Dose 3<br>Participants will receive orforglipron orally. | Drug: Orforglipron<br>* Administered orally.<br>* Other names: LY3502970;|
| Placebo Comparator: Placebo<br>Participants will receive placebo orally. | Drug: Placebo<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Hemoglobin A1c (HbA1c) |  | Baseline, Week 40 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with an HbA1c target value of <7.0% (53 mmol/mol) |  | Week 40 | 
| Percentage of Participants with an HbA1c target value of ≤6.5% (48 mmol/mol) |  | Week 40 | 
| Change from Baseline in Fasting Serum Glucose |  | Baseline, Week 40 | 
| Percentage Change from Baseline in Body Weight |  | Baseline, Week 40 | 
| Change from Baseline in Body Weight |  | Baseline, Week 40 | 
| Change from Baseline in Daily Average 7-point Self-Monitored Blood Glucose (SMBG) |  | Baseline, Week 40 | 
| Change from Baseline in Systolic Blood Pressure (SBP) |  | Baseline, Week 40 | 
| Change from Baseline in Non-HDL Cholesterol |  | Baseline, Week 40 | 
| Percentage Change from Baseline in Triglycerides |  | Baseline, Week 40 | 
| Percentage of Participants Who Achieved Weight Loss of ≥5% |  | Week 40 | 
| Change from Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Domain Scores |  | Baseline, Week 40 |