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Trial · Interventional

CompletedPhase 3Registry data

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

Short name ACHIEVE-4

NCTNCT05803421 (opens ClinicalTrials.gov in a new tab)Other id18563Other idJ2A-MC-GZGSOther id2022-502833-25-00Other idU1111-1285-6821
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
2,749 participants (actual)
Sponsor
Eli Lilly and Company · Industry
Design
Randomized · Open label (no masking)
Countries
16 countries

United States, Argentina, Austria, Brazil, Czechia, Germany, Greece, India, Italy, Mexico, Puerto Rico, Romania, Slovakia, South Korea, Spain, Turkey (Türkiye)

Start
3 Apr 2023
Primary completion
16 Mar 2026
Completion
16 Mar 2026
First posted
7 Apr 2023
Last update posted
17 Apr 2026
Conditions
Type 2 Diabetes · Obesity · Overweight or Obesity · Overweight · Cardiovascular Diseases · Chronic Kidney Disease

Timeline

1 trial · 1 completed

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20232024202520262027
  1. Ph 3

    ACHIEVE-4

    NCT05803421

    3 Apr 2023 to 16 Mar 2026

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • OrforglipronDrug
  • Insulin GlargineDrug

Arms2

  • Experimental

    Orforglipron

    Participants will receive escalated doses of orforglipron orally.

  • Active comparator

    Insulin Glargine

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

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. 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)

    Registry description

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

Secondary outcomes(9)

  1. 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)

    Registry description

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

  2. Change from Baseline in Hemoglobin A1c (HbA1c)

    Time frame · Baseline, Week 52

    Registry description

    Change from Baseline in HbA1c

  3. Change from Baseline in Fasting Serum Glucose

    Time frame · Baseline, Week 52

    Registry description

    Change from Baseline in Fasting Serum Glucose

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

    Time frame · Baseline, Week 52

    Registry description

    Change from Baseline in Daily Average 7-point SMBG

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

    Time frame · Week 52

    Registry description

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

  6. Change from Baseline in Body Weight

    Time frame · Baseline, Week 52

    Registry description

    Change from Baseline in Body Weight

  7. Percent Change from Baseline Body Weight

    Time frame · Week 52

    Registry description

    Percent Change from Baseline Body Weight

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

    Time frame · Baseline, Week 52

    Registry description

    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.

  9. Pharmacokinetics (PK): Plasma Serum Concentrations of Orforglipron

    Time frame · Baseline through Week 52

    Registry description

    PK will be estimated based on the population PK model.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

No results are posted for this trial.

Completed trials do not always post results.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

Studies with results

1 study on this page

PubMed tag: none · 2026

5 results

Cardiovascular safety of orforglipron versus insulin glargine in adults with type 2 diabetes at increased cardiovascular risk (ACHIEVE-4): a phase 3, event-driven, randomised, open-label, non-inferiority, active comparator trial.

Klein et al. 2026Lancet (London, England)

PMID 42815506DOI 10.1016/s0140-6736(26)01865-9PUB-42815506

Full text at the publisher5 results
Publisher pageSee results (5)

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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

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