A Study of Daily Oral Orforglipron (LY3502970) Compared With Insulin Glargine in Participants With Type 2 Diabetes and Obesity or Overweight at Increased Cardiovascular Risk

Phase 3

Active, not recruiting

• Conditions: Type 2 Diabetes; Obesity; Overweight or Obesity; Overweight; Cardiovascular Diseases; Chronic Kidney Disease
• Interventions: Drug: Orforglipron; Drug: Insulin Glargine

• Registration Number: NCT05803421
• Lead Sponsor: Eli Lilly and Company

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-03-27
• Study First Submitted QC: 2023-03-27
• Study Start: 2023-04-03
• Study First Posted: 2023-04-07
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-01
• Last Update Posted: 2025-07-02
• Primary Completion: 2025-09
• Study Completion: 2026-01-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 2749

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Orforglipron	Orforglipron	Participants will receive escalated doses of orforglipron orally.
Insulin Glargine	Insulin Glargine	Participants will receive insulin glargine subcutaneously (SC). Doses will be individualized and titrated according to a treat-to-target algorithm.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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.
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

Trial Locations

Locations (349)

Alliance for Multispecialty Research, LLC; 🇺🇸 Knoxville, Tennessee, United States

Cahaba Research - Pelham; 🇺🇸 Pelham, Alabama, United States

Syed Research Consultants Llc; 🇺🇸 Sheffield, Alabama, United States

The Institute for Liver Health; 🇺🇸 Chandler, Arizona, United States

Aventiv Research; 🇺🇸 Mesa, Arizona, United States

Arizona Liver Health - Peoria; 🇺🇸 Peoria, Arizona, United States

Elite Clinical Studies, LLC; 🇺🇸 Phoenix, Arizona, United States

Absolute Clinical Research; 🇺🇸 Phoenix, Arizona, United States

Clinical Research Institute of Arizona (CRI) - Sun City West; 🇺🇸 Sun City West, Arizona, United States

Orange Grove Family Practice; 🇺🇸 Tucson, Arizona, United States

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