A Study of Orforglipron (LY3502970) Compared With Semaglutide in Participants With Type 2 Diabetes Inadequately Controlled With Metformin (ACHIEVE-3)

Lilly

Status and phase: Active, not recruiting; Phase 3

Conditions: Type 2 Diabetes

Treatments: Drug: Semaglutide; Drug: Orforglipron

Study type: Interventional

Funder types: Industry

Identifiers

NCT06045221

J2A-MC-GZGU (Other Identifier)

18565

U1111-1290-6014 (Other Identifier)

Details and patient eligibility

About

The main purpose of this study is to assess efficacy and safety of orforglipron compared with oral semaglutide in participants with Type 2 diabetes and inadequate glycemic control with metformin.The study will last around 61 weeks.

Enrollment: 1,576 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have Type 2 Diabetes
• Have HbA1c ≥7.0% (53 mmol/mol) to ≤10.5% (91 mmol/mol), as determined by the central laboratory at screening.
• Have been on stable diabetes treatment with metformin ≥1500 milligram (mg)/day during the 90 days prior to screening and maintained through randomization.
• Are of stable body weight (±5%) for at least 90 days prior to screening 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

Exclusion criteria

• Have Type 1 Diabetes
• Are currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema, for example, laser photocoagulation or intravitreal injections of anti-vascular endothelial growth factor inhibitors.
• Have a history of ketoacidosis or hyperosmolar state or coma within the last 6 months prior to screening, or between screening and randomization.
• Have a New York Heart Association functional classification IV congestive heart failure.
• Have an estimated glomerular filtration rate (eGFR) <45 milliliter/minute (mL/min)/1.73 square meter (m²) or lower than the country-specific threshold for discontinuing metformin therapy per local label as determined by the central laboratory at screening.
• Have a serum calcitonin level of ≥35 nanogram/Liter (ng/L), as determined by the central laboratory at screening.
• Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

1,576 participants in 4 patient groups

Orforglipron Dose 1

Experimental group

Description:

Participants will receive orforglipron orally.

Treatment:

Drug: Orforglipron

Orforglipron Dose 2

Experimental group

Description:

Participants will receive orforglipron orally.

Treatment:

Drug: Orforglipron

Semaglutide Dose 1

Active Comparator group

Description:

Participants will receive semaglutide orally.

Treatment:

Drug: Semaglutide

Semaglutide Dose 2

Active Comparator group

Description:

Participants will receive semaglutide orally.

Treatment:

Drug: Semaglutide