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

NCT05971940 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: 18564J2A-MC-GZGTU1111-1290-5157
• Study Type: interventional
• Target: 559
• Locations: 6 countries
• Sites: 89

Brief Summary

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.

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Percentage of Participants With an HbA1c Target Value of < 7.0% (53 mmol/Mol)

  Week 40

• Percentage of Participants With an HbA1c Target Value of ≤6.5% (48 mmol/Mol)

  Week 40

• Change From Baseline in Fasting Serum Glucose (FSG)

  Baseline, Week 40

• Percent Change From Baseline in Body Weight

  Baseline, Week 40

• Change From Baseline in Body Weight

  Baseline, Week 40

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Participants received once daily (QD) doses of orforglipron-matching placebo capsules administered orally, over a period of 40 weeks.

Drug: Placebo

3 mg Orforglipron

EXPERIMENTAL

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

12 mg Orforglipron

EXPERIMENTAL

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

36 mg Orforglipron

EXPERIMENTAL

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

Interventions

Orforglipron DRUG

Administered orally

Also known as: LY3502970

12 mg Orforglipron; 3 mg Orforglipron; 36 mg Orforglipron

Placebo DRUG

Administered orally

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (89)

Syed Research Consultants Llc

Sheffield, Alabama, 35660, United States

Location

Epic Medical Research - Surprise

Surprise, Arizona, 85378, United States

Location

Quality of Life Medical & Research Center

Tucson, Arizona, 85712, United States

Location

Neighborhood Healthcare Institute of Health

Escondido, California, 92025, United States

Location

Velocity Clinical Research, Huntington Park

Huntington Park, California, 90255, United States

Location

Ark Clinical Research

Long Beach, California, 90815, United States

Location

Velocity Clinical Research, Westlake

Los Angeles, California, 90057, United States

Location

Infinity Clinical Research - Norco

Norco, California, 92860, United States

Location

Norcal Endocrinology & Internal Medicine

San Ramon, California, 94583, United States

Location

University Clinical Investigators, Inc.

Tustin, California, 92780, United States

Location

Connecticut Clinical Research - Cromwell

Cromwell, Connecticut, 06416, United States

Location

Invictus Clinical Research Group

Coconut Creek, Florida, 33073, United States

Location

Hillcrest Medical Research

DeLand, Florida, 32720, United States

Location

K2 Medical Research

Maitland, Florida, 32751, United States

Location

Global Health Research Center, Inc.

Miami Lakes, Florida, 33016, United States

Location

West Orange Endocrinology

Ocoee, Florida, 34761, United States

Location

Clinical Research Atlanta

Stockbridge, Georgia, 30281, United States

Location

Rophe Adult and Pediatric Medicine/SKYCRNG

Union City, Georgia, 30291, United States

Location

Family First Medical Center

Idaho Falls, Idaho, 83404, United States

Location

American Health Network of Indiana, LLC - Muncie

Muncie, Indiana, 47304, United States

Location

Tekton Research - Wichita

Wichita, Kansas, 67218, United States

Location

Alliance for Multispecialty Research, LLC

New Orleans, Louisiana, 70119, United States

Location

Revival Research Institute

Dearborn, Michigan, 48126, United States

Location

Billings Clinic

Billings, Montana, 59101, United States

Location

Ellipsis Research Group - Brooklyn - 7th Street

Brooklyn, New York, 11215, United States

Location

Central New York Clinical Research

Manlius, New York, 13104, United States

Location

Monroe Biomedical Research

Monroe, North Carolina, 28112, United States

Location

Lucas Research - New Bern

New Bern, North Carolina, 28562, United States

Location

Centricity Research Dublin Multispecialty

Dublin, Ohio, 43016, United States

Location

Alliance for Multispecialty Research, LLC

Norman, Oklahoma, 73069, United States

Location

The Corvallis Clinic, P.C.

Corvallis, Oregon, 97330, United States

Location

Preferred Primary Care Physicians, Preferred Clinical Research-St. Clair

Pittsburgh, Pennsylvania, 15243, United States

Location

Preferred Primary Care Physicians

Uniontown, Pennsylvania, 15401, United States

Location

The Research Center of The Upstate

Greenville, South Carolina, 29607, United States

Location

MDFirst Research, LLC

Lancaster, South Carolina, 29720, United States

Location

The Jackson Clinic

Jackson, Tennessee, 38305, United States

Location

Velocity Clinical Research, Dallas

Dallas, Texas, 75230, United States

Location

Juno Research

Houston, Texas, 77040, United States

Location

Endocrine Ips, Pllc

Houston, Texas, 77079, United States

Location

Amir A Hassan, MD, PA

Houston, Texas, 77089, United States

Location

Burke Internal Medicine and Research

Burke, Virginia, 22015, United States

Location

Wannan Medical College Yijishan Hospital

Wuhu, Anhui, 241001, China

Location

Luhe Hospital

Beijing, Beijing Municipality, 100000, China

Location

Beijing Hospital

Beijing, Beijing Municipality, 100730, China

Location

Beijing Pinggu District Hospital

Beijing, Beijing Municipality, 101200, China

Location

Shunde Hospital of Southern Medical Univesity

Foshan, Guangdong, 528399, China

Location

Huizhou Municipal Central Hospital

Huizhou, Guangdong, 516001, China

Location

The Fourth Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, 150001, China

Location

Nanyang First People's Hospital

Nanyang, Henan, 473001, China

Location

The Second Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450014, China

Location

Nanjing First Hospital

Nanjing, Jiangsu, 210006, China

Location

The Second Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, 210011, China

Location

Affiliated Hospital of Jiangsu University

Zhenjiang, Jiangsu, 212000, China

Location

Jinan Central Hospital

Jinan, Shandong, 250013, China

Location

Pudong New Area People's Hospital Shanghai

Shanghai, Shanghai Municipality, 201200, China

Location

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

Location

GMERS Medical College and General Hospital

Vadodara, Gujarat, 390021, India

Location

M S Ramaiah Medical College and Hospitals

Bangalore, Karnataka, 560054, India

Location

Medstar Speciality Hospital

Bangalore, Karnataka, 560092, India

Location

BSES MG Hospital

Mumbai, Maharashtra, 400058, India

Location

All India Institute of Medical Sciences (AIIMS) - Nagpur

Nagpur, Maharashtra, 441108, India

Location

Grant Medical Foundation - Ruby Hall Clinic

Pune, Maharashtra, 411001, India

Location

Madras Diabetes Research Foundation

Chennai, Tamil Nadu, 600086, India

Location

Kumudini Devi Diabetes Research Center

Hyderabad, Telangana, 500072, India

Location

Institute of Post Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital

Kolkata, West Bengal, 700020, India

Location

Tokuyama Clinic

Mihama-ku,Chiba City, Chiba, 261-0004, Japan

Location

Steel Memorial Yahata Hospital

Kitakyushu, Fukuoka, 805-8508, Japan

Location

Hasegawa Medical Clinic

Chitose, Hokkaido, 066-0032, Japan

Location

MinamiAkatsukaClinic

Mito, Ibaraki, 311-4153, Japan

Location

Iwamoto Clinic

Zentsujichó, Kagawa-ken, 765-0071, Japan

Location

Hayashi Diabetes Internal Medicine Clinic

Chigasaki, Kanagawa, 253-0044, Japan

Location

Medical Corporation Yuga Tsuruma Kaneshiro Diabetes Clinic

Yamato-shi, Kanagawa, 242-0004, Japan

Location

Medical Corporation Heishinkai OCROM Clinic

Suita-shi, Osaka, 565-0853, Japan

Location

The Institute of Medical Science, Asahi Life Foundation

Chuo-ku, Tokyo, 103-0002, Japan

Location

Tokyo-Eki Center-building Clinic

Chuo-ku, Tokyo, 103-0027, Japan

Location

Fukuwa Clinic

Chuo-ku, Tokyo, 104-0031, Japan

Location

Heishinkai Medical Group ToCROM Clinic

Shinjuku-ku, Tokyo, 160-0008, Japan

Location

Morinaga Ueno Clinic

Kumamoto, 860-0863, Japan

Location

Abe Clinic

Ōita, 870-0039, Japan

Location

Unidad de Investigaci�n Cl�nica Cardiometabolica de Occidente

Guadalajara, Jalisco, 44150, Mexico

Location

Centro de Investigacion Medica Integral

Guadalajara, Jalisco, 44160, Mexico

Location

Salud Cardiovascular

Guadalajara, Jalisco, 44860, Mexico

Location

Centro de Investigacion Medica de Occidente, S.C.

Zapopan, Jalisco, 44260, Mexico

Location

Investigacion En Salud Y Metabolismo S.C / Nutricion Clinica / Unidad de Base de Datos

Chihuahua City, 31110, Mexico

Location

PanAmerican Clinical Research - Querétaro - Avenida Antea

Querétaro, 76100, Mexico

Location

Instituto Veracruzano en Investigación Clínica S.C.

Veracruz, 91851, Mexico

Location

FAICIC S. de R.L. de C.V.

Veracruz, 91900, Mexico

Location

Puerto Rico Health Institute

Dorado, 00646, Puerto Rico

Location

Advance Medical Research Center

San Juan, 00926, Puerto Rico

Location

Related Publications (1)

• 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.

  PMID: 40544435 DERIVED

Related Links

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

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

orforglipron

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2023
• First Posted: August 2, 2023
• Study Start: August 9, 2023
• Primary Completion: April 3, 2025
• Study Completion: April 3, 2025
• Last Updated: April 22, 2026
• Results First Posted: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

ME (8); PR (2); CN (15); IN (9); US (41); JP (14)