NCT05803421CompletedPhase 3
A Phase 3, Open-Label Study of Once Daily LY3502970 Compared With Insulin Glargine in Adult Participants With Type 2 Diabetes and Obesity or Overweight at Increased Cardiovascular Risk
Eli Lilly and Company705 sites in 1 country2,749 target enrollmentStarted: April 3, 2023Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Eli Lilly and Company
- Enrollment
- 2,749
- Locations
- 705
- Primary Endpoint
- Time to First Occurrence of Any Major Adverse Cardiovascular Event (MACE-4) [Myocardial Infarction (MI), Stroke, Hospitalization for Unstable Angina, or Cardiovascular (CV) Death]
Study Overview
Brief Summary
The main purpose of this study is to determine safety and efficacy of orforglipron compared with insulin glargine in participants with type 2 diabetes and obesity or overweight at increased cardiovascular risk. The study will last approximately 2 years may include up to 27 visits.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Have been diagnosed with type 2 diabetes mellitus (T2DM)
- •Are at least 18 years of age or legal age of consent in the jurisdiction in which the study is taking place, whichever is older.
- •Have HbA1c at screening
- •≥7.0% and ≤10.5% if background diabetes medication does not include a sulfonylurea, or
- •≥7.5% and ≤10.5% if background diabetes medication includes a sulfonylurea.
- •Are on stable treatment of at least 1 and no more than 3 oral antihyperglycemic drugs for at least 90 days before screening. Antihyperglycemic drugs may include metformin, SGLT-2 inhibitors, and/or sulfonylureas
- •Have increased risk for cardiovascular (CV) events due to:
- •Coronary heart disease
- •Peripheral arterial disease, presumed to be of atherosclerotic origin
- •Cerebrovascular disease, presumed to be of atherosclerotic origin
- •Chronic kidney disease (CKD)
- •Congestive heart failure (CHF) New York Heart Association (NYHA) functional classification II to III
- •Are of stable weight (± 5%) for at least 90 days prior to screening
- •Have a BMI ≥25 kilograms per meter squared (kg/m2) at screening
Exclusion Criteria
- •Have type 1 diabetes mellitus
- •Have had chronic or acute pancreatitis any time prior to screening
- •Currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema (e.g. laster photocoagulation or intravitreal injections of anty-VEGF inhibitors
- •Have a known clinically significant gastric emptying abnormality
- •Have acute or chronic hepatitis, signs and symptoms of any other liver disease, or blood alanine transaminase (ALT) or aspartate aminotransferase (AST) enzyme level ≥5.0 times the upper limit of normal (ULN) for the reference range, as determined by the central laboratory
- •Have had any of the following within 60 days prior to screening: acute myocardial infarction, cerebrovascular accident (stroke), or hospitalization for congestive heart failure
- •Have an eGFR <15 mL/min/1.73 m2 as determined at screening
- •Have a family (first-degree relative) or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
- •Have been taking any other diabetes medicines other than metformin, SGLT-2 inhibitors, and/or sulfonylureas during the last 90 days
- •Have used any weight loss drugs, including herbal or nutritional supplements, within 90 days of screening
Arms & Interventions
Orforglipron
Experimental
Participants will receive escalated doses of orforglipron orally.
Intervention: Orforglipron (Drug)
Insulin Glargine
Active Comparator
Participants will receive insulin glargine subcutaneously (SC). Doses will be individualized and titrated according to a treat-to-target algorithm.
Intervention: Insulin Glargine (Drug)
Outcomes
Primary Outcomes
Time to First Occurrence of Any Major Adverse Cardiovascular Event (MACE-4) [Myocardial Infarction (MI), Stroke, Hospitalization for Unstable Angina, or Cardiovascular (CV) Death]
Time Frame: Baseline to End of the Study (Approximate Maximum 104 Weeks)
Time to First Occurrence of Any MACE-4 (Myocardial Infarction (MI), Stroke, Hospitalization for Unstable Angina, or Cardiovascular \[CV\] Death)
Secondary Outcomes
- Time to First Occurrence of Any MACE-3 Event (MI, Stroke, or CV death)(Baseline to End of the Study (Approximately 104 Weeks))
- Change from Baseline in Daily Average 7-point Self-monitoring Blood Glucose (SMBG) Profile(Baseline, Week 52)
- Percentage of Participants with HbA1c Target Values Less Than (<)7.0% (53 mmol/mol)(Week 52)
- Change from Baseline in Body Weight(Baseline, Week 52)
- Percent Change from Baseline Body Weight(Week 52)
- Change from Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Domain Score(Baseline, Week 52)
- Pharmacokinetics (PK): Plasma Serum Concentrations of Orforglipron(Baseline through Week 52)
- Change from Baseline in Hemoglobin A1c (HbA1c)(Baseline, Week 52)
- Change from Baseline in Fasting Serum Glucose(Baseline, Week 52)
Investigators
Study Sites (705)
Loading locations...
Similar Trials
Completed
Phase 3
A Study of Orforglipron (LY3502970) Compared With Semaglutide in Participants With Type 2 Diabetes Inadequately Controlled With MetforminType 2 DiabetesNCT06045221Eli Lilly and Company1,698
Completed
Phase 3
A Study of Orforglipron (LY3502970) Compared With Dapagliflozin in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With MetforminType 2 DiabetesNCT06192108Eli Lilly and Company962
Completed
Phase 3
A Study of Orforglipron (LY3502970) in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise AloneType 2 DiabetesNCT05971940Eli Lilly and Company559
Completed
Phase 3
A Study of Orforglipron in Adult Participants With Obesity or Overweight and Type 2 DiabetesOverweightObesityType 2 DiabetesNCT05872620Eli Lilly and Company1,613
Completed
Phase 3
A Study of Once-Daily Oral Orforglipron (LY3502970) in Japanese Adult Participants With Obesity DiseaseObesityNCT05931380Eli Lilly and Company238