A Study of Orforglipron (LY3502970) in Participants With Type 2 Diabetes and Inadequate Glycemic Control With Insulin Glargine, With or Without Metformin and/or SGLT-2 Inhibitor

Study Overview
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Brief Summary
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The main purpose of this study is to determine the safety and efficacy of orforglipron. Participants will have Type 2 Diabetes (T2D) and have inadequate glycemic control with insulin glargine with or without metformin and/or SGLT-2 (sodium-glucose cotransporter-2) inhibitor. The study will last about 46 weeks and may include up to 20 visits.

Official Title
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A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once Daily Oral Orforglipron Compared With Placebo in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Insulin Glargine, With or Without Metformin and/or SGLT-2 Inhibitor

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 (T2D) Have HbA1c ≥7.0% [53 mmol/mol] to ≤10.5% [91 mmol/mol] Have been treated with stable doses of the same formulation of the following for ≥90 days prior to screening visit 1 and have maintained the same doses through randomization: insulin glargine U-100 (100 U/mL) ≥0.25 U/kg/QD (units per kilogram per day) or ≥20 U/QD alone, or insulin glargine U-100 (100 U/mL) ≥0.25 U/kg/QD or ≥20 U/QD in combination with metformin, or SGLT-2 inhibitor, or both metformin and SGLT-2 inhibitor. Are of stable body weight (±5%) for at least 90 days prior to screening visit 1 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 kg/m^2 at baseline. Exclusion Criteria: Have New York Heart Association functional classification III-IV congestive heart failure. Have had any of the following cardiovascular conditions within 60 days prior to baseline. acute myocardial infarction cerebrovascular accident (stroke), or hospitalization for congestive heart failure. Have acute or chronic hepatitis, including a history of autoimmune hepatitis, signs or symptoms of any other liver disease other than nonalcoholic fatty liver disease Have had chronic or acute pancreatitis any time.

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 |
| --- | --- | --- |
| Orforglipron Dose 1, 2: Change from Baseline in Hemoglobin A1c (HbA1c) |  | Baseline, Week 40 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Orforglipron Dose 3: Change from Baseline in HbA1c |  | Baseline, Week 40 | 
| Percentage of Participants Who Achieved HbA1c <7.0% (53 millimoles per mole (mmol/mol)) |  | Baseline to Week 40 | 
| Percentage of Participants Who Achieved HbA1c ≤6.5% (48 mmol/mol) |  | Baseline to 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 | 
| Percentage Change from Baseline in non-HDL (non-high-density lipoprotein) Cholesterol |  | Baseline, Week 40 | 
| Percentage Change from Baseline in Triglycerides |  | Baseline, Week 40 | 
| Change from Baseline in Systolic Blood Pressure |  | Baseline, Week 40 | 
| Change from Baseline in Daily Insulin Glargine Dose |  | Baseline, Week 40 | 
| Percentage of Participants Who Achieved Weight Loss of ≥5% |  | Baseline to Week 40 | 
| Percentage of Participants Who Achieved Weight Loss of ≥10% |  | Baseline to Week 40 | 
| Percentage of Participants Who Achieved Weight Loss of ≥15% from Baseline |  | Baseline to Week 40 | 
| Change from Baseline in Short Form 36-Version 2 (SF-36v2) Acute Form Domain and Summary Scores |  | Baseline, Week 40 |