ACHIEVE-4

CompletedPhase 3

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

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

Lead sponsor

Eli Lilly and Company

Asset

Orforglipron

Oral · GLP-1 agonist

Listed sites

358

Recruiting sites

—

Enrollment

2,749

actual

Study population

Cardiovascular disease, Obesity / overweight, Type 2 diabetes

Key I/E criterion

•BMI ≥25

Primary endpoint

•4-point MACE (Myocardial infarction (any), Stroke (any), Unstable angina hospitalization, Cardiovascular death)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT05803421

Org study ID18563

Secondary ID2022-502833-25-00EU Trial Number

Secondary IDJ2A-MC-GZGSEli Lilly and Company

Secondary IDU1111-1285-6821Universal Trial Number (UTN)

Timeline

Milestones

Study start2023-04-03actual

Study first posted2023-04-07actual

Primary completion2026-03-16actual

Study completion2026-03-16actual

Last update posted2026-04-17actual

Assets

Investigational agents

Orforglipron

Study populations

Who this study enrolls

Cardiovascular diseaseObesity / overweightType 2 diabetes

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

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

Endpoints (10)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Glycemic / diabetes

Cardiovascular outcomes

Weight & body composition

Patient-reported / QoL

Safety / tolerability / PK

Cardiovascular outcomes

2 endpoints

Primary/protocol endpoint

Time to First Occurrence of Any Major Adverse Cardiovascular Event (MACE-4) [Myocardial Infarction (MI), Stroke, Hospitalization for Unstable Angina, or Cardiovascular (CV) Death]

Time frame:Baseline to End of the Study (Approximate Maximum 104 Weeks)

4-point MACE

time to event, event

componentsMyocardial infarction (any), Stroke (any), Unstable angina hospitalization, Cardiovascular death

Secondary/protocol endpoint

Time to First Occurrence of Any MACE-3 Event (MI, Stroke, or CV death)

Time frame:Baseline to End of the Study (Approximately 104 Weeks)

3-point MACE

time to event, event

componentsCardiovascular death, Non-fatal MI, Non-fatal stroke

Weight & body composition

2 endpoints

Secondary/protocol endpoint

Change from Baseline in Body Weight

Time frame:Baseline, Week 52

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Percent Change from Baseline Body Weight

Time frame:Week 52

Body weight, % change

percent change from baseline, improvement

Glycemic / diabetes

4 endpoints

Secondary/protocol endpoint

Change from Baseline in Hemoglobin A1c (HbA1c)

Time frame:Baseline, Week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change from Baseline in Fasting Serum Glucose

Time frame:Baseline, Week 52

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change from Baseline in Daily Average 7-point Self-monitoring Blood Glucose (SMBG) Profile

Time frame:Baseline, Week 52

change from baseline, improvement

Secondary/protocol endpoint

Percentage of Participants with HbA1c Target Values Less Than (<)7.0% (53 mmol/mol)

Time frame:Week 52

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Patient-reported / QoL

1 endpoint

Secondary/protocol endpoint

Change from Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Domain Score

Time frame:Baseline, Week 52

change from baseline, improvement

Safety / tolerability / PK

1 endpoint

Secondary/protocol endpoint

Pharmacokinetics (PK): Plasma Serum Concentrations of Orforglipron

Time frame:Baseline through Week 52

Plasma concentration (steady state)

concentration, descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.