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

NCT05803421
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Phase
Phase 3
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Recruitment status
Completed
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Participants
2,749
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Lead sponsor
Eli Lilly and Company
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Start date
2023-04-03
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Number of sites
358
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Summary
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.
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Acronym
ACHIEVE-4
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Short title
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
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Official title
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
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Completed
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Phase
Phase 3
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Study type
Interventional
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Completion date
2026-03-16
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First posted
2023-04-07
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Registry last updated
2026-04-17
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Primary completion date
2026-03-16
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Start date
2023-04-03
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Actual participants
2,749
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Participants
2,749
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Participant count basis
Actual
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Protocol amendments
2
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Number of sites
358
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Eli Lilly and Company
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05803421
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ClinicalTrials.gov ID
NCT05803421
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  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]

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

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

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

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

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

  2. Change from Baseline in Hemoglobin A1c (HbA1c)

    Timeframe: Baseline, Week 52

    Change from Baseline in HbA1c

  3. Change from Baseline in Fasting Serum Glucose

    Timeframe: Baseline, Week 52

    Change from Baseline in Fasting Serum Glucose

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

    Timeframe: Baseline, Week 52

    Change from Baseline in Daily Average 7-point SMBG

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

    Timeframe: Week 52

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

  6. Change from Baseline in Body Weight

    Timeframe: Baseline, Week 52

    Change from Baseline in Body Weight

  7. Percent Change from Baseline Body Weight

    Timeframe: Week 52

    Percent Change from Baseline Body Weight

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

    Timeframe: Baseline, Week 52

    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

    Timeframe: Baseline through Week 52

    PK will be estimated based on the population PK model.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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

  • 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
Sources for eligibility
clinicaltrials.gov

  • Alliance for Multispecialty Research, LLCDaphne, United States
  • Alliance for Multispecialty Research, LLCMobile, United States
  • Cahaba Research - PelhamPelham, United States
  • Syed Research Consultants LlcSheffield, United States
  • The Institute for Liver HealthChandler, United States
  • Aventiv ResearchMesa, United States
  • Arizona Liver Health - PeoriaPeoria, United States
  • Elite Clinical Studies, LLCPhoenix, United States
  • Absolute Clinical ResearchPhoenix, United States
  • Clinical Research Institute of Arizona (CRI) - Sun City WestSun City West, United States
  • Alliance for Multispecialty Research, LLCTempe, United States
  • Orange Grove Family PracticeTucson, United States
  • KLR Business Group, Inc. dba Arkansas Clinical ResearchLittle Rock, United States
  • Hope Clinical Research, Inc.Canoga Park, United States
  • Valley Clinical Trials, Inc.Covina, United States
  • Neighborhood Healthcare Institute of HealthEscondido, United States
  • Valley ResearchFresno, United States
  • Orange County Research CenterLake Forest, United States
  • Ark Clinical ResearchLong Beach, United States
  • Pacific Clinical StudiesLos Alamitos, United States
  • Velocity Clinical Research, Los AngelesLos Angeles, United States
  • Infinity Clinical Research - NorcoNorco, United States
  • Velocity Clinical Research, North HollywoodNorth Hollywood, United States
  • Valley Clinical Trials, Inc.Northridge, United States
  • Rancho Cucamonga Clinical ResearchRancho Cucamonga, United States

And 333 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2022-502833-25-00
  • J2A-MC-GZGS
  • U1111-1285-6821
Sources for references
clinicaltrials.gov

Related records

Drugs (2)

Lead sponsors (1)

Conditions (4)

Targets (1)