A Study of Orforglipron (LY3502970) in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone (ACHIEVE-1)

A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once Daily Oral LY3502970 Compared With Placebo in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone

The main purpose of this study is to determine safety and efficacy of orforglipron compared with placebo in adult participants with type 2 diabetes and inadequate glycemic control with diet and exercise alone. The study will last approximately 54 weeks.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Placebo; Drug: Orforglipron

• Study Type: Interventional
• Enrollment (Actual): 559
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Wuhu, Anhui, China, 241001
      • Wannan Medical College Yijishan Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100730
      • Beijing Hospital
    • Beijing, Beijing Municipality, China, 101200
      • Beijing Pinggu District Hospital
    • Beijing, Beijing Municipality, China, 100000
      • Luhe 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 Affiliated Hospital of Harbin Medical University
  • Henan
    • Nanyang, Henan, China, 473001
      • 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
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 201200
      • Pudong New Area People's Hospital Shanghai
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University
• India
  • Gujarat
    • Vadodara, Gujarat, India, 390021
      • GMERS Medical College and General Hospital
  • Karnataka
    • Bangalore, Karnataka, India, 560054
      • M S Ramaiah Medical College and Hospitals
    • Bangalore, Karnataka, India, 560092
      • Medstar Speciality Hospital
  • Maharashtra
    • Mumbai, Maharashtra, India, 400058
      • BSES MG hospital
    • Nagpur, Maharashtra, India, 441108
      • All India Institute of Medical Sciences (AIIMS) - Nagpur
    • Pune, Maharashtra, India, 411001
      • Grant Medical Foundation - Ruby Hall Clinic
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600086
      • Madras Diabetes Research Foundation
  • Telangana
    • Hyderabad, Telangana, India, 500072
      • Kumudini Devi Diabetes Research Center
  • West Bengal
    • Kolkata, West Bengal, India, 700020
      • Institute of Post Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital
• Japan
  • Kumamoto, Japan, 860-0863
    • Morinaga Ueno Clinic
  • Ōita, Japan, 870-0039
    • Abe Clinic
  • Chiba
    • Mihama-ku,Chiba City, Chiba, Japan, 261-0004
      • Tokuyama Clinic
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan, 805-8508
      • Steel Memorial Yahata Hospital
  • Hokkaido
    • Chitose, Hokkaido, Japan, 066-0032
      • Hasegawa Medical Clinic
  • Ibaraki
    • Mito, Ibaraki, Japan, 311-4153
      • MinamiAkatsukaClinic
  • Kagawa-ken
    • Zentsujichó, Kagawa-ken, Japan, 765-0071
      • Iwamoto Clinic
  • Kanagawa
    • Chigasaki, Kanagawa, Japan, 253-0044
      • Hayashi Diabetes Internal Medicine Clinic
    • Yamato-shi, Kanagawa, Japan, 242-0004
      • Medical Corporation Yuga Tsuruma Kaneshiro Diabetes Clinic
  • Osaka
    • Suita-shi, Osaka, Japan, 565-0853
      • Medical Corporation Heishinkai OCROM Clinic
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 103-0027
      • Tokyo-Eki Center-building Clinic
    • Chuo-ku, Tokyo, Japan, 104-0031
      • Fukuwa Clinic
    • Chuo-ku, Tokyo, Japan, 103-0002
      • The Institute of Medical Science, Asahi Life Foundation
    • Shinjuku-ku, Tokyo, Japan, 160-0008
      • Heishinkai Medical Group ToCROM Clinic
• Mexico
  • Chihuahua City, Mexico, 31110
    • Investigacion En Salud Y Metabolismo S.C / Nutricion Clinica / Unidad de Base de Datos
  • Querétaro, Mexico, 76100
    • PanAmerican Clinical Research - Querétaro - Avenida Antea
  • Veracruz, Mexico, 91900
    • FAICIC S. de R.L. de C.V.
  • Veracruz, Mexico, 91851
    • Instituto Veracruzano en Investigación Clínica S.C.
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44150
      • Unidad de Investigaci�n Cl�nica Cardiometabolica de Occidente
    • Guadalajara, Jalisco, Mexico, 44860
      • Salud Cardiovascular
    • Guadalajara, Jalisco, Mexico, 44160
      • Centro de Investigacion Medica Integral
    • Zapopan, Jalisco, Mexico, 44260
      • Centro de Investigacion Medica de Occidente, S.C.
• Puerto Rico
  • Dorado, Puerto Rico, 00646
    • Puerto Rico Health Institute
  • San Juan, Puerto Rico, 00926
    • Advance Medical Research Center
• United States
  • Alabama
    • Sheffield, Alabama, United States, 35660
      • Syed Research Consultants LLC
  • Arizona
    • Surprise, Arizona, United States, 85378
      • Epic Medical Research - Surprise
    • Tucson, Arizona, United States, 85712
      • Quality of Life Medical & Research Center
  • California
    • Escondido, California, United States, 92025
      • Neighborhood Healthcare Institute of Health
    • Huntington Park, California, United States, 90255
      • Velocity Clinical Research, Huntington Park
    • Long Beach, California, United States, 90815
      • ARK Clinical Research
    • Los Angeles, California, United States, 90057
      • Velocity Clinical Research, Westlake
    • Norco, California, United States, 92860
      • Infinity Clinical Research - Norco
    • San Ramon, California, United States, 94583
      • Norcal Endocrinology & Internal Medicine
    • Tustin, California, United States, 92780
      • University Clinical Investigators, Inc.
  • Connecticut
    • Cromwell, Connecticut, United States, 06416
      • Connecticut Clinical Research - Cromwell
  • Florida
    • Coconut Creek, Florida, United States, 33073
      • Invictus Clinical Research Group
    • DeLand, Florida, United States, 32720
      • Hillcrest Medical Research
    • Maitland, Florida, United States, 32751
      • K2 Medical Research
    • Miami Lakes, Florida, United States, 33016
      • Global Health Research Center, Inc.
    • Ocoee, Florida, United States, 34761
      • West Orange Endocrinology
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Atlanta
    • Union City, Georgia, United States, 30291
      • Rophe Adult and Pediatric Medicine/SKYCRNG
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Family First Medical Center
  • Indiana
    • Muncie, Indiana, United States, 47304
      • American Health Network of Indiana, LLC - Muncie
  • Kansas
    • Wichita, Kansas, United States, 67218
      • Tekton Research - Wichita
  • Louisiana
    • New Orleans, Louisiana, United States, 70119
      • Alliance for Multispecialty Research, LLC
  • Michigan
    • Dearborn, Michigan, United States, 48126
      • Revival Research Institute
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic
  • New York
    • Brooklyn, New York, United States, 11215
      • Ellipsis Research Group - Brooklyn - 7th Street
    • Manlius, New York, United States, 13104
      • Central New York Clinical Research
  • North Carolina
    • Monroe, North Carolina, United States, 28112
      • Monroe Biomedical Research
    • New Bern, North Carolina, United States, 28562
      • Lucas Research - New Bern
  • Ohio
    • Dublin, Ohio, United States, 43016
      • Centricity Research Dublin Multispecialty
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Alliance for Multispecialty Research, LLC
  • Oregon
    • Corvallis, Oregon, United States, 97330
      • The Corvallis Clinic, P.C.
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15243
      • Preferred Primary Care Physicians, Preferred Clinical Research-St. Clair
    • Uniontown, Pennsylvania, United States, 15401
      • Preferred Primary Care Physicians
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • The Research Center of The Upstate
    • Lancaster, South Carolina, United States, 29720
      • MDFirst Research, LLC
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • The Jackson Clinic
  • Texas
    • Dallas, Texas, United States, 75230
      • Velocity Clinical Research, Dallas
    • Houston, Texas, United States, 77040
      • Juno Research
    • Houston, Texas, United States, 77079
      • Endocrine Ips, Pllc
    • Houston, Texas, United States, 77089
      • Amir A Hassan, MD, PA
  • Virginia
    • Burke, Virginia, United States, 22015
      • Burke Internal Medicine and Research

Participation Criteria

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 ≤9.5% (80 mmol/mol) despite diet and exercise treatment, as determined by the central laboratory at screening.
• Are naïve to insulin therapy except for gestational diabetes or ≤14 days use for acute treatment and have not used any oral or injectable antihyperglycemic medications during the 90 days preceding screening or between screening and randomization.
• Are of stable 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.
• Have a body mass index (BMI) ≥23.0 kilogram/square meter (kg/m²) at screening.

Exclusion Criteria:

• Have Type 1 Diabetes
• Have a history of ketoacidosis or hyperosmolar state or coma within the last 6 months prior to screening, or between screening and randomization.
• Currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema
• Have New York Heart Association functional classification IV congestive heart failure.
• Have acute or chronic pancreatitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received once daily (QD) doses of orforglipron-matching placebo capsules administered orally, over a period of 40 weeks.	Drug: Placebo; Administered orally
Experimental: 3 mg Orforglipron; Participants received orforglipron capsules administered orally QD, starting at 1 milligram (mg) and increasing by 1 mg every 4 weeks until reaching a targeted dose of 3 mg, which was then maintained up to week 40.	Drug: Orforglipron; Administered orally; Other Names: LY3502970
Experimental: 12 mg Orforglipron; Participants received orforglipron capsules administered orally QD, starting at 1 mg and increasing every 4 weeks until reaching a targeted dose of 12 mg, which was then maintained up to week 40.	Drug: Orforglipron; Administered orally; Other Names: LY3502970
Experimental: 36 mg Orforglipron; Participants received orforglipron capsules administered orally QD, starting at 1 mg and increasing every 4 weeks until reaching a targeted dose of 36 mg, which was then maintained up to week 40.	Drug: Orforglipron; Administered orally; Other Names: LY3502970

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HbA1c	Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A, measured to reflect average plasma glucose concentration over prolonged periods of time.; Values represented under "Least Squares (LS) Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a mixed-model repeated measures (MMRM) with analysis country, treatment by time, baseline by time by treatment, and strata by time by treatment in the model. Strata was defined by joint levels of baseline HbA1c (≤ [less than or equal to] 8.0%, > [greater than] 8.0%) and prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured.	Baseline, Week 40

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With an HbA1c Target Value of < 7.0% (53 mmol/Mol)	Percentage of participants with an HbA1c target value of less than (<) 7.0% (53 millimoles per mole [mmol/mol]) was analysed by Logistic regression with analysis country, treatment by baseline and treatment by strata in the model. Strata were defined by joint levels of baseline HbA1c (≤8.0%, >8.0%) and prior use of any antihyperglycemic medication (yes or no).	Week 40
Percentage of Participants With an HbA1c Target Value of ≤6.5% (48 mmol/Mol)	Percentage of Participants with an HbA1c target value of less than or equal to (≤) 6.5% (48 mmol/mol) was analysed by Logistic regression with analysis country, treatment by baseline and treatment by strata in the model. Strata were defined by joint levels of baseline HbA1c (≤8.0%, >8.0%) and prior use of any antihyperglycemic medication (yes or no).	Week 40
Change From Baseline in Fasting Serum Glucose (FSG)	Values represented under "Least Squares (LS) Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a mixed-model repeated measures (MMRM) with analysis country, treatment by time, baseline by time by treatment, and strata by time by treatment in the model. Strata was defined by joint levels of baseline HbA1c (≤ [less than or equal to] 8.0%, > [greater than] 8.0%) and prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured.	Baseline, Week 40
Percent Change From Baseline in Body Weight	Values represented under "LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a MMRM with analysis country, treatment by time, baseline by time by treatment, and strata by time by treatment in the model. Strata was defined by joint levels of baseline HbA1c (≤8.0%, >8.0%) and prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured.	Baseline, Week 40
Change From Baseline in Body Weight	Values represented under "LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a MMRM with analysis country, treatment by time, baseline by time by treatment, and strata by time by treatment in the model. Strata was defined by joint levels of baseline HbA1c (≤8.0%, >8.0%) and prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured.	Baseline, Week 40
Percent Change From Baseline in Non-High-Density Lipoprotein (Non-HDL) Cholesterol	Values represented under "Geometric LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a MMRM with analysis : log (Actual Measurement/Baseline) = country, treatment by time, log(baseline) by time by treatment, and strata by time by treatment in the model. Strata were defined by joint levels of baseline HbA1c (≤8.0%, >8.0%) and prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured.	Baseline, Week 40
Percent Change From Baseline in Triglycerides	Values represented under "Geometric LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a MMRM with analysis : log (Actual Measurement/Baseline) = country, treatment by time, log(baseline) by time by treatment, and strata by time by treatment in the model. Strata were defined by joint levels of baseline HbA1c (≤8.0%, >8.0%) and prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured.	Baseline, Week 40
Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG)	The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Post meal, Midday Premeal, Midday 2-hour Post meal, Evening Premeal, Evening 2-hour Post meal and Bedtime. The daily average was calculated as the average of the 7 blood glucose values collected on a particular day. Values represented under "LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a MMRM with analysis country, treatment by time, baseline by time by treatment, and strata by time by treatment in the model. Strata was defined by joint levels of baseline HbA1c (≤8.0%, >8.0%) and prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured.	Baseline, Week 40
Percentage of Participants With Greater Than or Equal to (≥) 5% Body Weight Reduction	Percentage of participants with ≥5% body weight reduction was analysed by Logistic regression with analysis country, treatment by baseline and treatment by strata in the model. Strata were defined by joint levels of baseline HbA1c (≤8.0%, >8.0%) and prior use of any antihyperglycemic medication (yes or no).	Week 40
Change From Baseline in Systolic Blood Pressure (SBP)	Values represented under "LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a MMRM with analysis country, treatment by time, baseline by time by treatment, and strata by time by treatment in the model. Strata was defined by joint levels of baseline HbA1c (≤8.0%, >8.0%) and prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured.	Baseline, Week 40
Change From Baseline in Short Form-36 Health Survey Version 2 (SF-36v2) Acute Form (Physical-Component and Mental-Component) Scores	The SF-36v2 is a participant-reported measure designed to assess health status using 36 items across 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The physical functioning domain assesses limitations due to health "now," whereas the remaining domains assess functioning "in the past week." Each domain is scored individually, and information from these 8 domains is aggregated into 2 health component summary scores, the Physical Component Summary and Mental Component Summary. Items are answered on Likert scales of varying lengths (3-point, 5-point, or 6-point scales). Scoring of each domain and both summary scores are norm based and presented in the form of T-scores, with a mean of 50 and a standard deviation of 10. Higher scores indicate better levels of function and/or better health. Range cannot be specified in norm-based scores.	Baseline, Week 40

Collaborators and Investigators

• 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

General Publications

• Rosenstock J, Hsia S, Nevarez Ruiz L, Eyde S, Cox D, Wu WS, Liu R, Li J, Fernandez Lando L, Denning M, Ludwig L, Chen Y; ACHIEVE-1 Trial Investigators. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes. N Engl J Med. 2025 Sep 18;393(11):1065-1076. doi: 10.1056/NEJMoa2505669. Epub 2025 Jun 21.

Helpful Links

• A Study of Orforglipron (LY3502970) in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone (ACHIEVE-1)

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2023
• Primary Completion (Actual): April 3, 2025
• Study Completion (Actual): April 3, 2025

Study Registration Dates

• First Submitted: July 25, 2023
• First Submitted That Met QC Criteria: July 25, 2023
• First Posted (Actual): August 2, 2023

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; orforglipron
• Other Study ID Numbers: 18564; J2A-MC-GZGT (Other Identifier: Eli Lilly and Company); U1111-1290-5157 (Other Identifier: UTN Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual participant 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