A Study of Orforglipron (LY3502970) Compared With Semaglutide in Participants With Type 2 Diabetes Inadequately Controlled With Metformin (ACHIEVE-3)

September 19, 2025 updated by: Eli Lilly and Company

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

1698

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Córdoba, Argentina, 5003DCE
        • Instituto Medico Damic
      • Córdoba, Argentina, 5000
        • Instituto de Investigaciones Clínicas Córdoba
      • Santiago del Estero, Argentina, 4200
        • Sanatorio Norte
    • Buenos Aires
      • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, 1056
        • Centro de Investigaciones Metabólicas (CINME)
      • Lanús, Buenos Aires, Argentina, B1824KAJ
        • CIMeL
      • Mar del Plata, Buenos Aires, Argentina, 7600
        • Centro de Investigaciones Medicas Mar del Plata
      • Mar del Plata, Buenos Aires, Argentina, 7600
        • Policlinica Red OMIP
    • Buenos Aires F.D.
      • Buenos Aires, Buenos Aires F.D., Argentina, C1120AAC
        • Centro Medico Viamonte
      • Buenos Aires, Buenos Aires F.D., Argentina, 1405
        • Consultorio de Investigacion Clinica EMO SRL
      • Buenos Aires, Buenos Aires F.D., Argentina, C1061AAS
        • CIPREC
      • CABA, Buenos Aires F.D., Argentina, 1204
        • Instituto Centenario
    • La Pampa Province
      • Santa Rosa, La Pampa Province, Argentina, 6300
        • Centro de Salud e Investigaciones Médicas
    • Santa Fe Province
      • Rosario, Santa Fe Province, Argentina, 2000
        • Instituto Médico Fundación Grupo Colaborativo Rosario Investigación y Prevención Medica
      • Rosario, Santa Fe Province, Argentina, 2000
        • INECO Neurociencias Oroño
      • Rosario, Santa Fe Province, Argentina, 2000
        • Instituto de Especialidades de la Salud Rosario
      • Rosario, Santa Fe Province, Argentina, 2000
        • Instituto Medico Catamarca Imec
      • Rosario, Santa Fe Province, Argentina, S2000DEJ
        • Fundacion Estudios Clinicos
  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 101200
        • Beijing Pinggu District Hospital
    • Chongqing Municipality
      • Chongqing, Chongqing Municipality, China, 400014
        • Chongqing General Hospital
    • Guangdong
      • Foshan, Guangdong, China, 528399
        • Shunde Hospital of Southern Medical Univesity
      • Huizhou, Guangdong, China, 516001
        • Huizhou Municipal Central Hospital
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150001
        • The Fourth Hospital of Harbin Medical University
    • Henan
      • Luoyang Shi, Henan, China, 471003
        • The First Affiliated Hospital of Henan University of Science &Technology
      • Nanyang, Henan, China, 473014
        • Nanyang First People's Hospital
      • Zhengzhou, Henan, China, 450014
        • The Second Affiliated Hospital of Zhengzhou University
    • Jiangsu
      • Nanjing, Jiangsu, China, 210006
        • Nanjing First Hospital
      • Nanjing, Jiangsu, China, 210011
        • The Second Affiliated Hospital of Nanjing Medical University
      • Zhenjiang, Jiangsu, China, 212000
        • Affiliated Hospital of Jiangsu University
    • Jiangxi
      • Pingxiang, Jiangxi, China, 337055
        • Jiangxi Pingxiang People's Hospital
    • Liaoning
      • Dalian, Liaoning, China, 116033
        • Dalian Municipal Central Hospital Affiliated of Dalian Medical University
    • Shandong
      • Jinan, Shandong, China, 250013
        • Jinan Central Hospital
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200030
        • Shanghai Sixth People's Hospital
      • Shanghai, Shanghai Municipality, China, 201200
        • Pudong New Area People's Hospital Shanghai
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • West China Hospital of Sichuan University
    • Yunnan
      • Kunming, Yunnan, China, 650032
        • First Affiliated Hospital of Kunming Medical University
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310013
        • Zhejiang Hospital
      • Huzhou, Zhejiang, China, 313000
        • Huzhou Central Hospital
      • Wenzhou, Zhejiang, China, 325000
        • The First Affiliated Hospital of Wenzhou Medical University
  • Japan
      • Gifu, Japan, 501-1112
        • Gifu University Hospital
    • Ehime
      • Matsuyama, Ehime, Japan, 116099
        • Mikannohana Clinic, Diabetes, Endocrinology and Metabolism
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 060-0062
        • Manda Memorial Hospital
    • Ibaraki
      • Mito, Ibaraki, Japan, 310-0826
        • Nakamoto Internal Medicine Clinic
      • Naka, Ibaraki, Japan, 311-0113
        • Nakakinen Clinic
      • Tsuchiura, Ibaraki, Japan, 300-0835
        • Ohishi Internal Medicine Clinic
    • Kanagawa
      • Kamakura-shi, Kanagawa, Japan, 247-0056
        • Takai Internal Medicine Clinic
    • Osaka
      • Kashihara, Osaka, Japan, 582-0005
        • Shiraiwa Medical Clinic
    • Tokyo
      • Ootaku, Tokyo, Japan, 143-0015
        • Medical Corporation Sato Medical clinic
  • Mexico
      • Durango, Mexico, 34000
        • Lahoja. Asociacion Para La Investigacion Y La Farmacovigilancia
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44600
        • Instituto Jalisciense de Investigacion en Diabetes y Obesidad
      • Guadalajara, Jalisco, Mexico, 44670
        • Private Practice - Dr. Arechavaleta Granell Maria del Rosario
      • Guadalajara, Jalisco, Mexico, 44670
        • Virgen Cardiovascular Research SC
      • Guadalajara, Jalisco, Mexico, 44160
        • Centro de Investigacion Medica Integral
      • Guadalajara, Jalisco, Mexico, 44670
        • CICEJ Centro de Investigación Clínica Endocrinológica de Jalisco S.C
      • Zapopan, Jalisco, Mexico, 44260
        • Centro de Investigacion Medica de Occidente, S.C.
    • Mexico City
      • Mexico City, Mexico City, Mexico, 06760
        • Caimed Investigacion En Salud S.A. de C.V.
      • Mexico City, Mexico City, Mexico, 11650
        • Centro Especializado En Diabetes, Obesidad Y Prevencion De Enfermedades Cardiovasculares
    • Nuevo León
      • Monterrey, Nuevo León, Mexico, 64460
        • Unidad Biomedica Avanzada Monterrey
      • Monterrey, Nuevo León, Mexico, 66460
        • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
      • Monterrey, Nuevo León, Mexico, 64610
        • Clínica García Flores SC
      • Monterrey, Nuevo León, Mexico, 64718
        • Eukarya PharmaSite
      • Monterrey, Nuevo León, Mexico, 64060
        • Cardiolink Clin Trials
      • San Nicolás de los Garza, Nuevo León, Mexico, 66465
        • Centro de investigación y control metabólico
    • Sinaloa
      • Culiacán, Sinaloa, Mexico, 80230
        • Centro para el Desarrollo de la Medicina y de Asistencia Medica Especializada S.C.
  • Puerto Rico
      • Ponce, Puerto Rico, 00717
        • Research and Cardiovascular Corp.
      • San Juan, Puerto Rico, 00909
        • Latin Clinical Trial Center
    • PR
      • Guaynabo, PR, Puerto Rico, 00968
        • Isis Clinical Research Center
      • San Juan, PR, Puerto Rico, 00921
        • Mgcendo Llc
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85051
        • Absolute Clinical Research
    • California
      • Canoga Park, California, United States, 91304
        • San Fernando Valley Health Institute
      • Escondido, California, United States, 92025
        • Neighborhood Healthcare Institute of Health
      • Gardena, California, United States, 90247
        • Velocity Clinical Research, Gardena
      • Los Angeles, California, United States, 90057
        • Velocity Clinical Research, Westlake
      • Los Angeles, California, United States, 90035
        • Biopharma Informatic, LLC
      • Norco, California, United States, 92860
        • Infinity Clinical Research - Norco
      • Northridge, California, United States, 91325
        • Valley Clinical Trials, Inc.
      • San Ramon, California, United States, 94583
        • Norcal Endocrinology & Internal Medicine
      • Spring Valley, California, United States, 91978
        • Encompass Clinical Research
      • Tustin, California, United States, 92780
        • University Clinical Investigators, Inc.
    • Colorado
      • Golden, Colorado, United States, 80401
        • New West Physicians Clinical Research
    • Connecticut
      • Cromwell, Connecticut, United States, 06416
        • Connecticut Clinical Research - Cromwell
    • Florida
      • Clearwater, Florida, United States, 33765
        • Clinical Research of West Florida, Inc. (Clearwater)
      • Margate, Florida, United States, 33063
        • South Florida Clinical Research Institute
      • Miami, Florida, United States, 33176
        • Miami Dade Medical Research Institute, LLC
      • Ocoee, Florida, United States, 34761
        • West Orange Endocrinology
      • Tamarac, Florida, United States, 33321
        • Latin Clinical Trial Center Florida
      • Tampa, Florida, United States, 33606
        • Clinical Research of West Florida
      • West Palm Beach, Florida, United States, 33401
        • Metabolic Research Institute, Inc.
    • Georgia
      • Lawrenceville, Georgia, United States, 30046
        • Balanced Life Health Care Solutions/SKYCRNG
      • Stockbridge, Georgia, United States, 30281
        • Clinical Research Atlanta
      • Woodstock, Georgia, United States, 30189
        • North Georgia Clinical Research
    • Idaho
      • Boise, Idaho, United States, 83704
        • Northwest Clinical Trials
      • Idaho Falls, Idaho, United States, 83404
        • Family First Medical Center
    • Indiana
      • Greenfield, Indiana, United States, 46140
        • American Health Network of Indiana, LLC - Greenfield
      • Valparaiso, Indiana, United States, 46383
        • Velocity Clinical Research, Valparaiso
    • Kansas
      • Topeka, Kansas, United States, 66606
        • Cotton O'Neil Diabetes & Endocrinology
      • Wichita, Kansas, United States, 67218
        • Tekton Research, Inc
    • Louisiana
      • New Orleans, Louisiana, United States, 70115
        • DelRicht Research
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Joslin Diabetes Center
    • Michigan
      • Dearborn, Michigan, United States, 48126
        • Revival Research Institute, LLC
    • Mississippi
      • Ridgeland, Mississippi, United States, 39157
        • SKY Integrative Medical Center/SKYCRNG
    • Missouri
      • Kansas City, Missouri, United States, 64131
        • Kansas City Research Institute
    • Montana
      • Kalispell, Montana, United States, 59901
        • Logan Health Research
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • Wr-Crcn, Llc
    • New Jersey
      • Trenton, New Jersey, United States, 08611
        • Premier Research
    • New York
      • Albany, New York, United States, 12203
        • Albany Medical College, Division of Community Endocrinology
      • Brooklyn, New York, United States, 11215
        • Ellipsis Research Group - Brooklyn - 7th Street
      • Westfield, New York, United States, 14787
        • Great Lakes Medical Research, LLC
    • North Carolina
      • Greensboro, North Carolina, United States, 27408
        • PharmQuest Life Sciences, LLC
      • Morehead City, North Carolina, United States, 28557
        • Lucas Research, Inc
      • Statesville, North Carolina, United States, 28625
        • Accellacare - Piedmont
      • Winston-Salem, North Carolina, United States, 27104
        • Wake Forest University Baptist Medical Center (WFUBMC)
    • Ohio
      • Columbus, Ohio, United States, 43213
        • Aventiv Research Inc
    • Oklahoma
      • Moore, Oklahoma, United States, 73160
        • Tekton Research, Inc
      • Norman, Oklahoma, United States, 73069
        • Alliance for Multispecialty Research, LLC
    • Oregon
      • Corvallis, Oregon, United States, 97330
        • The Corvallis Clinic, P.C.
    • Pennsylvania
      • Beaver, Pennsylvania, United States, 15009
        • Heritage Valley Medical Group, Inc.
      • Pittsburgh, Pennsylvania, United States, 15236
        • Preferred Primary Care Physicians, Preferred Clinical Research (Ofc 18)
    • South Carolina
      • Greenville, South Carolina, United States, 29607
        • The Research Center of The Upstate
    • Tennessee
      • Knoxville, Tennessee, United States, 37909
        • New Phase Research and Development
      • Memphis, Tennessee, United States, 38119
        • Clinical Neuroscience Solutions Inc.
    • Texas
      • Austin, Texas, United States, 78759
        • Velocity Clinical Research, Austin
      • Dallas, Texas, United States, 75230
        • Velocity Clinical Research, Dallas
      • Fort Worth, Texas, United States, 76132
        • Diabetes and Thyroid Center of Ft. Worth
      • Houston, Texas, United States, 77040
        • Juno Research
      • Houston, Texas, United States, 77079
        • Endocrine Ips, Pllc
      • Houston, Texas, United States, 77089
        • Clear Brook Medical Associates
      • Mesquite, Texas, United States, 75149
        • Southern Endocrinology Associates
      • Weslaco, Texas, United States, 78596
        • Texas Valley Clinical Research
    • Utah
      • Salt Lake City, Utah, United States, 84106
        • Synexus Clinical Research US, Inc.
    • Washington
      • Redmond, Washington, United States, 98052
        • Eastside Research Associates
      • Renton, Washington, United States, 98057
        • Rainier Clinical Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Orforglipron Dose 1
Participants will receive orforglipron orally.
Drug: Orforglipron
Administered orally
Other Names:
  • LY3502970
Experimental: Orforglipron Dose 2
Participants will receive orforglipron orally.
Drug: Orforglipron
Administered orally
Other Names:
  • LY3502970
Active Comparator: Semaglutide Dose 1
Participants will receive semaglutide orally.
Drug: Semaglutide
Administered orally
Active Comparator: Semaglutide Dose 2
Participants will receive semaglutide orally.
Drug: Semaglutide
Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change from Baseline in Hemoglobin A1c (HbA1c)
Time Frame: Baseline, Week 52
Baseline, Week 52

Secondary Outcome Measures

Outcome Measure
Time Frame
Change from Baseline in Systolic Blood Pressure (SBP)
Time Frame: Baseline, Week 52
Baseline, Week 52
Change from Baseline in Body Weight
Time Frame: Baseline, Week 52
Baseline, Week 52
Change from Baseline in Fasting Serum Glucose
Time Frame: Baseline, Week 52
Baseline, Week 52
Change from Baseline in HbA1c
Time Frame: Baseline, Week 52
Baseline, Week 52
Percentage of Participants Who Achieved HbA1c <7.0% 53 millimole/mole (mmol/mol)
Time Frame: Week 52
Week 52
Percentage of Participants Who Achieved HbA1c ≤6.5% (48 mmol/mol)
Time Frame: Week 52
Week 52
Percentage Change from Baseline in Body Weight
Time Frame: Baseline, Week 52
Baseline, Week 52
Percentage of Participants Who Achieved HbA1c <5.7% (39 mmol/mol)
Time Frame: Week 52
Week 52
Change from Baseline in Daily Average 7-point Self-monitored Blood Glucose (SMBG)
Time Frame: Baseline, Week 52
Baseline, Week 52
Percentage of Participants Who Achieved Weight Loss of ≥5%
Time Frame: Week 52
Week 52
Percentage of Participants Who Achieved Weight Loss of ≥10%
Time Frame: Week 52
Week 52
Percentage of Participants Who Achieved Weight Loss of ≥15%
Time Frame: Week 52
Week 52
Change from Baseline in Diastolic Blood Pressure (DBP)
Time Frame: Baseline, Week 52
Baseline, Week 52
Percentage Change from Baseline in Total Cholesterol
Time Frame: Baseline, Week 52
Baseline, Week 52
Percentage Change from Baseline in High Density Lipoprotein (HDL)-Cholesterol
Time Frame: Baseline, Week 52
Baseline, Week 52
Percentage Change from Baseline in Low Density Lipoprotein (LDL)-Cholesterol
Time Frame: Baseline, Week 52
Baseline, Week 52
Percentage Change from Baseline in Very Low Density Lipoprotein (VLDL)-Cholesterol
Time Frame: Baseline, Week 52
Baseline, Week 52
Percentage Change from Baseline in Non-HDL-Cholesterol
Time Frame: Baseline, Week 52
Baseline, Week 52
Percentage Change from Baseline in Triglycerides
Time Frame: Baseline, Week 52
Baseline, Week 52
Change from Baseline in Short Form 36 Version 2 (SF-36-v2) Acute Form Domain Summary Scores
Time Frame: Baseline, Week 52
Baseline, Week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eli Lilly and Company

Investigators

  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 22, 2023

Primary Completion (Actual)

August 22, 2025

Study Completion (Actual)

August 22, 2025

Study Registration Dates

First Submitted

September 13, 2023

First Submitted That Met QC Criteria

September 13, 2023

First Posted (Actual)

September 21, 2023

Study Record Updates

Last Update Posted (Actual)

September 22, 2025

Last Update Submitted That Met QC Criteria

September 19, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18565
  • J2A-MC-GZGU (Other Identifier: Eli Lilly and Company)
  • U1111-1290-6014 (Other Identifier: UTN Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

IPD Sharing 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.

IPD Sharing Access Criteria

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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