Cardiovascular Diseases, Chronic Kidney Disease, Obesity, Overweight, Overweight or Obesity, Type 2 Diabetes
Conditions
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.
Interventions
DRUGOrforglipron
Administered orally once daily
DRUGInsulin Glargine
Administered SC once daily
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Occurrence of Any Major Adverse Cardiovascular Event (MACE-4) [Myocardial Infarction (MI), Stroke, Hospitalization for Unstable Angina, or Cardiovascular (CV) Death] | 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
| Measure | Time frame | Description |
|---|---|---|
| Time to First Occurrence of Any MACE-3 Event (MI, Stroke, or CV death) | Baseline to End of the Study (Approximately 104 Weeks) | Time to First Occurrence of Any MACE-3 Event (MI, Stroke, or CV death) |
| Change from Baseline in Hemoglobin A1c (HbA1c) | Baseline, Week 52 | Change from Baseline in HbA1c |
| Change from Baseline in Fasting Serum Glucose | Baseline, Week 52 | Change from Baseline in Fasting Serum Glucose |
| Change from Baseline in Daily Average 7-point Self-monitoring Blood Glucose (SMBG) Profile | Baseline, Week 52 | Change from Baseline in Daily Average 7-point SMBG |
| Percentage of Participants with HbA1c Target Values Less Than (<)7.0% (53 mmol/mol) | Week 52 | Percentage of Participants with HbA1c Target Values \<7.0% (53 mmol/mol) |
| Change from Baseline in Body Weight | Baseline, Week 52 | Change from Baseline in Body Weight |
| Percent Change from Baseline Body Weight | Week 52 | Percent Change from Baseline Body Weight |
| Change from Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Domain Score | Baseline, Week 52 | The SF-36v2 acute form is a 36-item generic, participant completed measure designed to assess 8 domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Scores of each domain are measured by T-scores, with a mean of 50 and standard deviation of 10; higher scores indicate better levels of function and/or better health. |
| Pharmacokinetics (PK): Plasma Serum Concentrations of Orforglipron | Baseline through Week 52 | PK will be estimated based on the population PK model. |
Countries
Argentina, Austria, Brazil, Czechia, Germany, Greece, India, Italy, Mexico, Puerto Rico, Romania, Slovakia, South Korea, Spain, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORCall 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Outcome results
None listed