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Completed

NCT Number: NCT06045221

A Study of Orforglipron (LY3502970) Compared With Semaglutide in Participants With Type 2 Diabetes Inadequately Controlled With Metformin

The main purpose of this study is to assess efficacy and safety of orforglipron compared with oral semaglutide in participants with Type 2 diabetes and inadequate glycemic control with metformin.The study will last around 61 weeks.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Centro de Investigaciones Metabólicas (CINME), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Have Type 2 Diabetes
  • Have HbA1c ≥7.0% (53 mmol/mol) to ≤10.5% (91 mmol/mol), as determined by the central laboratory at screening.
  • Have been on stable diabetes treatment with metformin ≥1500 milligram (mg)/day during the 90 days prior to screening and maintained through randomization.
  • Are of stable body weight (±5%) for at least 90 days prior to screening and agree to not initiate an intensive diet or exercise program during the study with the intent of reducing body weight, other than the lifestyle and/or dietary measures for diabetes treatment

Exclusion criteria

  • Have Type 1 Diabetes
  • Are currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema, for example, laser photocoagulation or intravitreal injections of anti-vascular endothelial growth factor inhibitors.
  • Have a history of ketoacidosis or hyperosmolar state or coma within the last 6 months prior to screening, or between screening and randomization.
  • Have a New York Heart Association functional classification IV congestive heart failure.
  • Have an estimated glomerular filtration rate (eGFR) <45 milliliter/minute (mL/min)/1.73 square meter (m²) or lower than the country-specific threshold for discontinuing metformin therapy per local label as determined by the central laboratory at screening.
  • Have a serum calcitonin level of ≥35 nanogram/Liter (ng/L), as determined by the central laboratory at screening.
  • Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years.

Treatment and study plan

Orforglipron

Drug

Administered orally

Other names: LY3502970

semaglutide

Drug

Administered orally

Primary outcomes

  1. Change from Baseline in Hemoglobin A1c (HbA1c)

    Time frame: Baseline, Week 52

Secondary outcomes

  1. Change from Baseline in HbA1c

    Time frame: Baseline, Week 52

  2. Percentage of Participants Who Achieved HbA1c <7.0% 53 millimole/mole (mmol/mol)

    Time frame: Week 52

  3. Percentage of Participants Who Achieved HbA1c ≤6.5% (48 mmol/mol)

    Time frame: Week 52

  4. Percentage Change from Baseline in Body Weight

    Time frame: Baseline, Week 52

  5. Change from Baseline in Body Weight

    Time frame: Baseline, Week 52

  6. Percentage of Participants Who Achieved HbA1c <5.7% (39 mmol/mol)

    Time frame: Week 52

  7. Change from Baseline in Fasting Serum Glucose

    Time frame: Baseline, Week 52

  8. Change from Baseline in Daily Average 7-point Self-monitored Blood Glucose (SMBG)

    Time frame: Baseline, Week 52

  9. Percentage of Participants Who Achieved Weight Loss of ≥5%

    Time frame: Week 52

  10. Percentage of Participants Who Achieved Weight Loss of ≥10%

    Time frame: Week 52

  11. Percentage of Participants Who Achieved Weight Loss of ≥15%

    Time frame: Week 52

  12. Change from Baseline in Systolic Blood Pressure (SBP)

    Time frame: Baseline, Week 52

  13. Change from Baseline in Diastolic Blood Pressure (DBP)

    Time frame: Baseline, Week 52

  14. Percentage Change from Baseline in Total Cholesterol

    Time frame: Baseline, Week 52

  15. Percentage Change from Baseline in High Density Lipoprotein (HDL)-Cholesterol

    Time frame: Baseline, Week 52

  16. Percentage Change from Baseline in Low Density Lipoprotein (LDL)-Cholesterol

    Time frame: Baseline, Week 52

  17. Percentage Change from Baseline in Very Low Density Lipoprotein (VLDL)-Cholesterol

    Time frame: Baseline, Week 52

  18. Percentage Change from Baseline in Non-HDL-Cholesterol

    Time frame: Baseline, Week 52

  19. Percentage Change from Baseline in Triglycerides

    Time frame: Baseline, Week 52

  20. Change from Baseline in Short Form 36 Version 2 (SF-36-v2) Acute Form Domain Summary Scores

    Time frame: Baseline, Week 52

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

A Phase 3, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Once Daily Oral LY3502970 Compared With Oral Semaglutide in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin (ACHIEVE-3)

Acronym: ACHIEVE-3

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Sep 21, 2023
Registry last updated
Sep 22, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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