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

ClinicalTrials17 Apr 2026·Phase 3● 8/10i

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 Company

Phase 3 open-label trial compared once-daily oral orforglipron versus insulin glargine in people with type 2 diabetes and obesity or overweight at increased cardiovascular risk. The study enrolled 2,749 participants with primary endpoint of time to first major adverse cardiovascular event, completed in March 2026. Eli Lilly is positioning orforglipron as a cardiovascular outcomes option in high-risk populations, directly competing with established insulin therapy in this indication. This represents the first cardiovascular outcomes trial for orforglipron following its April 2026 FDA approval for type 2 diabetes.

Strategic signal

Eli Lilly positioned orforglipron against insulin glargine rather than GLP-1 competitors, targeting the high-risk cardiovascular population where insulin remains standard care. This head-to-head design against insulin differentiates orforglipron's evidence package from Novo's oral semaglutide, which lacks dedicated cardiovascular outcomes data in this population. The completed trial timing aligns with orforglipron's recent FDA approval, providing immediate post-launch cardiovascular data. This strategy mirrors tirzepatide's approach of establishing cardiovascular credentials early in the commercial lifecycle.

GLP-1Type 2 diabetesWeight lossCardiovascularEli Lilly

Original Abstract

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. | Condition(s): Type 2 Diabetes; Obesity; Overweight or Obesity; Overweight; Cardiovascular Diseases | Primary endpoint(s): Time to First Occurrence of Any Major Adverse Cardiovascular Event (MACE-4) [Myocardial Infarction (MI), Stroke, Hospitalization for Unstable Angina, or Cardiovascular (CV) Death] | Enrollment: 2,749 (actual) | Phase: Phase 3 | Sponsor: Eli Lilly and Company | Expected completion: 2026-03-16 | Status: Completed | Last update: 2026-04-17

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