Type 2 DiabetesPhase 3ACHIEVE-1NCT05971940
A Study of Orforglipron (LY3502970) in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone
A Phase 3 study testing Orforglipron in people with Type 2 Diabetes, run by Eli Lilly and Company at 89 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Orforglipron
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 559 participants
- Where
- 89 sitesin 6 countries
- Study dates
- 9 Aug 2023to 3 Apr 2025
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
89 sites in 6 countries.
89 sites in 6 countries
United States41 sites
Billings Clinic
Billings, Montana, 59101
Ellipsis Research Group - Brooklyn - 7th Street
Brooklyn, New York, 11215
Burke Internal Medicine and Research
Burke, Virginia, 22015
Invictus Clinical Research Group
Coconut Creek, Florida, 33073
The Corvallis Clinic, P.C.
Corvallis, Oregon, 97330
Connecticut Clinical Research - Cromwell
Cromwell, Connecticut, 06416
Velocity Clinical Research, Dallas
Dallas, Texas, 75230
Revival Research Institute
Dearborn, Michigan, 48126
Hillcrest Medical Research
DeLand, Florida, 32720
Centricity Research Dublin Multispecialty
Dublin, Ohio, 43016
Neighborhood Healthcare Institute of Health
Escondido, California, 92025
The Research Center of The Upstate
Greenville, South Carolina, 29607
Juno Research
Houston, Texas, 77040
Endocrine Ips, Pllc
Houston, Texas, 77079
Amir A Hassan, MD, PA
Houston, Texas, 77089
Velocity Clinical Research, Huntington Park
Huntington Park, California, 90255
Family First Medical Center
Idaho Falls, Idaho, 83404
The Jackson Clinic
Jackson, Tennessee, 38305
MDFirst Research, LLC
Lancaster, South Carolina, 29720
Ark Clinical Research
Long Beach, California, 90815
Velocity Clinical Research, Westlake
Los Angeles, California, 90057
K2 Medical Research
Maitland, Florida, 32751
Central New York Clinical Research
Manlius, New York, 13104
Global Health Research Center, Inc.
Miami Lakes, Florida, 33016
Monroe Biomedical Research
Monroe, North Carolina, 28112
American Health Network of Indiana, LLC - Muncie
Muncie, Indiana, 47304
Lucas Research - New Bern
New Bern, North Carolina, 28562
Alliance for Multispecialty Research, LLC
New Orleans, Louisiana, 70119
Infinity Clinical Research - Norco
Norco, California, 92860
Alliance for Multispecialty Research, LLC
Norman, Oklahoma, 73069
West Orange Endocrinology
Ocoee, Florida, 34761
Preferred Primary Care Physicians, Preferred Clinical Research-St. Clair
Pittsburgh, Pennsylvania, 15243
Norcal Endocrinology & Internal Medicine
San Ramon, California, 94583
Syed Research Consultants Llc
Sheffield, Alabama, 35660
Clinical Research Atlanta
Stockbridge, Georgia, 30281
Epic Medical Research - Surprise
Surprise, Arizona, 85378
Quality of Life Medical & Research Center
Tucson, Arizona, 85712
University Clinical Investigators, Inc.
Tustin, California, 92780
Rophe Adult and Pediatric Medicine/SKYCRNG
Union City, Georgia, 30291
Preferred Primary Care Physicians
Uniontown, Pennsylvania, 15401
Tekton Research - Wichita
Wichita, Kansas, 67218
China15 sites
Luhe Hospital
Beijing, Beijing Municipality, 100000
Beijing Hospital
Beijing, Beijing Municipality, 100730
Beijing Pinggu District Hospital
Beijing, Beijing Municipality, 101200
West China Hospital of Sichuan University
Chengdu, Sichuan, 610041
Shunde Hospital of Southern Medical Univesity
Foshan, Guangdong, 528399
The Fourth Affiliated Hospital of Harbin Medical University
Harbin, Heilongjiang, 150001
Huizhou Municipal Central Hospital
Huizhou, Guangdong, 516001
Jinan Central Hospital
Jinan, Shandong, 250013
Nanjing First Hospital
Nanjing, Jiangsu, 210006
The Second Affiliated Hospital of Nanjing Medical University
Nanjing, Jiangsu, 210011
Nanyang First People's Hospital
Nanyang, Henan, 473001
Pudong New Area People's Hospital Shanghai
Shanghai, Shanghai Municipality, 201200
Wannan Medical College Yijishan Hospital
Wuhu, Anhui, 241001
The Second Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450014
Affiliated Hospital of Jiangsu University
Zhenjiang, Jiangsu, 212000
Japan14 sites
Hayashi Diabetes Internal Medicine Clinic
Chigasaki, Kanagawa, 253-0044
Hasegawa Medical Clinic
Chitose, Hokkaido, 066-0032
The Institute of Medical Science, Asahi Life Foundation
Chuo-ku, Tokyo, 103-0002
Tokyo-Eki Center-building Clinic
Chuo-ku, Tokyo, 103-0027
Fukuwa Clinic
Chuo-ku, Tokyo, 104-0031
Steel Memorial Yahata Hospital
Kitakyushu, Fukuoka, 805-8508
Morinaga Ueno Clinic
Kumamoto, 860-0863
Tokuyama Clinic
Mihama-ku,Chiba City, Chiba, 261-0004
MinamiAkatsukaClinic
Mito, Ibaraki, 311-4153
Abe Clinic
Ōita, 870-0039
Heishinkai Medical Group ToCROM Clinic
Shinjuku-ku, Tokyo, 160-0008
Medical Corporation Heishinkai OCROM Clinic
Suita-shi, Osaka, 565-0853
Medical Corporation Yuga Tsuruma Kaneshiro Diabetes Clinic
Yamato-shi, Kanagawa, 242-0004
Iwamoto Clinic
Zentsujichó, Kagawa-ken, 765-0071
India9 sites
M S Ramaiah Medical College and Hospitals
Bangalore, Karnataka, 560054
Medstar Speciality Hospital
Bangalore, Karnataka, 560092
Madras Diabetes Research Foundation
Chennai, Tamil Nadu, 600086
Kumudini Devi Diabetes Research Center
Hyderabad, Telangana, 500072
Institute of Post Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital
Kolkata, West Bengal, 700020
BSES MG Hospital
Mumbai, Maharashtra, 400058
All India Institute of Medical Sciences (AIIMS) - Nagpur
Nagpur, Maharashtra, 441108
Grant Medical Foundation - Ruby Hall Clinic
Pune, Maharashtra, 411001
GMERS Medical College and General Hospital
Vadodara, Gujarat, 390021
Mexico8 sites
Investigacion En Salud Y Metabolismo S.C / Nutricion Clinica / Unidad de Base de Datos
Chihuahua City, 31110
Unidad de Investigaci�n Cl�nica Cardiometabolica de Occidente
Guadalajara, Jalisco, 44150
Centro de Investigacion Medica Integral
Guadalajara, Jalisco, 44160
Salud Cardiovascular
Guadalajara, Jalisco, 44860
PanAmerican Clinical Research - Querétaro - Avenida Antea
Querétaro, 76100
Instituto Veracruzano en Investigación Clínica S.C.
Veracruz, 91851
FAICIC S. de R.L. de C.V.
Veracruz, 91900
Centro de Investigacion Medica de Occidente, S.C.
Zapopan, Jalisco, 44260
Puerto Rico2 sites
Puerto Rico Health Institute
Dorado, 00646
Advance Medical Research Center
San Juan, 00926
About this study
Official title: 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.
- Conditions
- Type 2 Diabetes
- Being tested
- Orforglipron, Placebo
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OrforglipronDrug
Also called LY3502970
Administered orally
PlaceboDrug
Administered orally
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants received once daily (QD) doses of orforglipron-matching placebo capsules administered orally, over a period of 40 weeks. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Orforglipron |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Week 40
Secondary outcomes (11)
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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: Baseline, Week 40
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2023
- Study start9 Aug 2023
- Primary completion3 Apr 2025
- Study completion3 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 559 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05971940
- Sponsor's protocol ID
- 18564
- Other IDs
- J2A-MC-GZGT, U1111-1290-5157
- Acronym
- ACHIEVE-1
- Status last verified
- Aug 2026
- First submitted
- 25 Jul 2023
- Last updated
- 3 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
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.
PubMed 40544435