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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)

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ClinicalTrials.gov Identifier: NCT05803421
Recruitment Status : Recruiting
First Posted : April 7, 2023
Last Update Posted : September 1, 2023
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Obesity Overweight or Obesity Overweight Cardiovascular Diseases Chronic Kidney Disease Drug: Orforglipron Drug: Insulin Glargine Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2620 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 3, 2023
Estimated Primary Completion Date : January 24, 2025
Estimated Study Completion Date : September 24, 2025

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Orforglipron
Participants will receive escalated doses of orforglipron orally.
 Drug: Orforglipron
Administered orally once daily
Other Name: LY3502970
Active Comparator: Insulin Glargine
Participants will receive insulin glargine subcutaneously (SC). Doses will be individualized and titrated according to a treat-to-target algorithm.
 Drug: Insulin Glargine
Administered SC once daily


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


Secondary Outcome Measures :
  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) ]
    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 ]
    Change from Baseline in HbA1c

  3. Change from Baseline in Fasting Serum Glucose [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: Week 52 ]
    Percentage of Participants with HbA1c Target Values <7.0% (53 mmol/mol)

  6. Change from Baseline in Body Weight [ Time Frame: Baseline, Week 52 ]
    Change from Baseline in Body Weight

  7. Percent Change from Baseline Body Weight [ Time Frame: Week 52 ]
    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 ]
    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 ]
    PK will be estimated based on the population PK model.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05803421


Contacts
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Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 ClinicalTrials.gov@lilly.com

Locations
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Sponsors and Collaborators
Eli Lilly and Company
Investigators
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Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
More Information
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Additional Information:

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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT05803421    
Other Study ID Numbers: 18563
J2A-MC-GZGS ( Other Identifier: Eli Lilly and Company )
2022-502833-25-00 ( Other Identifier: EU Trial Number )
U1111-1285-6821 ( Other Identifier: Universal Trial Number (UTN) )
First Posted: April 7, 2023    Key Record Dates
Last Update Posted: September 1, 2023
Last Verified: August 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: http://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Cardiovascular Diseases
Diabetes Mellitus
Obesity
Diabetes Mellitus, Type 2
Overweight
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Overnutrition
Nutrition Disorders
Body Weight
 Urologic Diseases
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Male Urogenital Diseases
Renal Insufficiency
Chronic Disease
Disease Attributes
Pathologic Processes
Insulin Glargine
Hypoglycemic Agents
Physiological Effects of Drugs