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 (ACHIEVE-4)

Lilly

Status and phase: Enrolling; Phase 3

Conditions: Chronic Kidney Disease; Overweight; Overweight or Obesity; Obesity; Cardiovascular Diseases; Type 2 Diabetes

Treatments: Drug: Orforglipron; Drug: Insulin Glargine

Study type: Interventional

Funder types: Industry

Identifiers

NCT05803421

2022-502833-25-00 (Other Identifier)

18563

U1111-1285-6821 (Other Identifier)

J2A-MC-GZGS (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 2,620 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,620 participants in 2 patient groups

Orforglipron

Experimental group

Description:

Participants will receive escalated doses of orforglipron orally.

Treatment:

Drug: Orforglipron

Insulin Glargine

Active Comparator group

Description:

Participants will receive insulin glargine subcutaneously (SC). Doses will be individualized and titrated according to a treat-to-target algorithm.

Treatment:

Drug: Insulin Glargine