Type 2 DiabetesPhase 3ACHIEVE-2NCT06192108
A Study of Orforglipron (LY3502970) Compared With Dapagliflozin in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin
A Phase 3 study testing Orforglipron and Dapagliflozin in people with Type 2 Diabetes, run by Eli Lilly and Company at 74 sites in 6 countries.
Trial summary
The main purpose of this study is to assess the safety and efficacy of orforglipron compared with dapagliflozin in improving blood sugar control in participants with type 2 diabetes (T2D) with inadequate glycemic control using metformin. The study will last approximately 46 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 and Dapagliflozin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 962 participants
- Where
- 74 sitesin 6 countries
- Study dates
- 10 Jan 2024to 26 Sep 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 a clinical diagnosis of T2D based on the World Health Organization classification or other locally applicable diagnostic standards.
- Have HbA1c ≥7.0% (53 mmol/mol) to ≤10.5% (91 mmol/mol) at screening.
- Have been on stable diabetes treatment with metformin ≥1500 milligram per day (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.
- Have a body mass index (BMI) ≥23.0 kilogram/square meter (kg/m²) at screening.
Who cannot join
- Have Type 1 Diabetes (T1D)
- Are currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema
- Have an estimated glomerular filtration rate (eGFR) <45 milliliter per minute (mL/min)/1.73 square meter (m2)
- Have acute or chronic hepatitis
- Have had chronic or acute pancreatitis any time.
- Have been treated with any antihyperglycemic medication (other than metformin) within the 90 days prior to screening.
Trial locations and contacts
74 sites in 6 countries.
74 sites in 6 countries
United States19 sites
Albuquerque Clinical Trials, Inc.
Albuquerque, New Mexico, 87102
St. Vincent Healthcare
Billings, Montana, 59101
Alliance Research Institute - Canoga Park
Canoga Park, California, 91304
Velocity Clinical Research, Dallas
Dallas, Texas, 75230
CMR of Greater New Haven, LLC
Hamden, Connecticut, 06517
Juno Research
Houston, Texas, 77040
Accellacare, US Inc., d/b/a Accellacare of Knoxville
Jefferson City, Tennessee, 37760
Accellacare - DuPage
Lombard, Illinois, 60148
Ark Clinical Research
Long Beach, California, 90815
Collaborative Neuroscience Research, LLC
Los Alamitos, California, 90720
Tandem Clinical Research
Marrero, Louisiana, 70072
Accellacare - Mt Pleasant
Mt. Pleasant, South Carolina, 29464
Alliance for Multispecialty Research, LLC
Norman, Oklahoma, 73069
Elite Clinical Trials
Rexburg, Idaho, 83440
Wolverine Clinical Trials
Santa Ana, California, 92706
Consano Clinical Research, LLC
Shavano Park, Texas, 78231
Institute of Endocrinology Diabetes, Health & Hormone
Stockbridge, Georgia, 30281
Essential Medical Research
Tulsa, Oklahoma, 74137
Accellacare - Winston-Salem
Winston-Salem, North Carolina, 27103
Mexico13 sites
Fundación Cardiovascular de Aguascalientes A.C.
Aguascalientes, 20230
Cryptex Investigación Clínica S.A. de C.V.
Cuauhtémoc, Ciudad de México, Mexico City, 06100
Instituto de Diabetes, Obesidad y Nutricion
Cuernavaca, Morelos, 62250
Centro Para El Desarrollo de La Medicina Y de Asistencia Medica Especializada S.C.
Culiacán, Sinaloa, 80230
Lahoja. Asociacion Para La Investigacion Y La Farmacovigilancia
Durango, 34000
Instituto Jalisciense de Investigacion en Diabetes y Obesidad
Guadalajara, Jalisco, 44600
ProcliniQ Investigación Clínica SA de CV
Mexico City, Mexico City, 14050
Cardiolink Clin Trials
Monterrey, Nuevo León, 64060
Clínica García Flores SC
Monterrey, Nuevo León, 64610
Grupo Ollin Care
Pachuca, Hidalgo, 42000
Servicios Integrales Nova de Monterrey S.A. de C.V.
San Nicolás de los Garza, Nuevo León, 66450
Consultorio de Medicina Especilizada del Sector Privado
Xalapa, Veracruz, 91193
Hospital Angeles Xalapa
Xalapa, Veracruz, 91193
China12 sites
The Fourth Affiliated Hospital of Harbin Medical University
Harbin, Heilongjiang, 150001
The Second People's Hospital of Hefei
Hefei, Anhui, 230011
Jinan Central Hospital
Jinan, Shandong, 250013
First Affiliated Hospital of Kunming Medical University
Kunming, Yunnan, 650032
Nanjing First Hospital
Nanjing, Jiangsu, 210006
The Second Affiliated Hospital of Nanjing Medical University
Nanjing, Jiangsu, 210011
The First Affiliated Hospital of Nanyang Medical College
Nanyang, Henan, 473007
Shanghai Sixth People's Hospital
Shanghai, Shanghai Municipality
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215006
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, 325000
The Second Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450014
Affiliated Hospital of Jiangsu University
Zhenjiang, Jiangsu, 212000
Germany11 sites
Diabetes- und Stoffwechselpraxis Bochum
Bochum, North Rhine-Westphalia, 44869
Zentrum fur klinische Forschung - Köln
Cologne, North Rhine-Westphalia, 51069
InnoDiab Forschung Gmbh
Essen, North Rhine-Westphalia, 45136
Medizentrum Essen Borbeck
Essen, North Rhine-Westphalia, 45355
Diabetes Zentrum Wilhelmsburg
Hamburg, 21109
Diabetologische Schwerpunktpraxis Dr. Staudenmeyer & Dr. Schiwietz
Lingen, Lower Saxony, 49808
CRS Clinical Research Services Mannheim
Mannheim, Baden-Wurttemberg, 68167
Institut für Diabetesforschung GmbH Münster
Münster, North Rhine-Westphalia, 48145
RED-Institut GmbH
Oldenburg in Holstein, Schleswig-Holstein, 23758
Praxis Dr. Veronika Wenzl-Bauer
Rehlingen, Saarland, 66780
Zentrum für klinische Studien
Saint Ingbert, Saarland, 66386
Poland11 sites
Zdrowie Osteo-Medic
Bialystok, Podlaskie Voivodeship, 15-351
Specderm Poznanska
Bialystok, Podlaskie Voivodeship, 15-375
NZOZ Centrum Medyczne KERmed
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-231
Medyczne Centrum Diabetologiczno Endokrynologiczno Metaboliczne DIAB-ENDO-MET
Krakow, Lesser Poland Voivodeship, 31-261
Centrum Terapii Wspolczesnej J. M. Jasnorzewska Spolka Komandytowo-Akcyjna
Lodz, Łódź Voivodeship, 90-338
Clinical Best Solutions
Lublin, Lublin Voivodeship, 20-011
CenterMed Lublin NZOZ
Lublin, Lublin Voivodeship, 20-044
Ekamed
Lublin, Lublin Voivodeship, 20-718
Centrum Medyczne "Diabetika"
Radom, Masovian Voivodeship, 26-600
Centrum Badań Klinicznych Piotr Napora lekarze sp.p.
Wroclaw, Lower Silesian Voivodeship, 50-162
Samodzielny Publiczny Szpital Kliniczny nr 1 SUM
Zabrze, Silesian Voivodeship, 41-800
Taiwan8 sites
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, 807
Kaohsiung Veterans General Hospital
Kaohsiung City, 81362
Chang Gung Memorial Hospital at Kaohsiung
Kaohsiung Niao Sung Dist, Kaohsiung, 83301
Fu Jen Catholic University Hospital
New Taipei City, 24352
Taichung Veterans General Hospital
Taichung, 407
National Cheng Kung University Hospital
Tainan, 704
National Taiwan University Hospital
Taipei, 10002
Taipei Veterans General Hospital
Taipei, 11217
About this study
Official title: A Phase 3, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Once Daily Oral Orforglipron Compared With Dapagliflozin in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin (ACHIEVE-2)
The main purpose of this study is to assess the safety and efficacy of orforglipron compared with dapagliflozin in improving blood sugar control in participants with type 2 diabetes (T2D) with inadequate glycemic control using metformin. The study will last approximately 46 weeks.
- Conditions
- Type 2 Diabetes
- Being tested
- Orforglipron, Dapagliflozin
- 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
DapagliflozinDrug
Administered orally
| Study group | Role | What they receive |
|---|---|---|
| Orforglipron 3 mg | Experimental | Participants received orforglipron, administered orally once daily (QD), starting at a dose of 1 milligram (mg) and escalated at week 4 to a dose of 3 mg, which was then maintained up to week 40. Receives: Drug: Orforglipron |
| Orforglipron 12 mg | Experimental | Participants received orforglipron, administered orally QD, starting at a dose of 1 mg and escalated every 4 weeks (to 3 mg at week 4 and 6 mg at week 8) until reaching a dose of 12 mg at week 12, which was then maintained up to week 40. Receives: Drug: Orforglipron |
| Orforglipron 36 mg | Experimental | Participants received orforglipron, administered orally QD, starting at a dose of 1 mg and escalated every 4 weeks (to 3 mg at week 4, 6 mg at week 8, 12 mg at week 12, and 24 mg at week 16) until reaching a dose of 36 mg at week 20, which was then maintained up to week 40. Receives: Drug: Orforglipron |
| Dapagliflozin 10 mg | Active comparator | Participants received dapagliflozin, administered orally QD, at a fixed dose of 10 mg starting at randomization, which was maintained up to week 40. Receives: Drug: Dapagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in HbA1c [Noninferiority Analysis]
- Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A, measured to reflect average plasma glucose concentration over a prolonged period of time.
- Values represented under "Least Squares (LS) Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE were calculated using a mixed-model repeated measures (MMRM) analysis for post-baseline measures, with country, baseline by time by treatment, and strata by time by treatment in the model. Strata were defined by joint levels of HbA1c level (<= [less than or equal to] 8.0% ,> [greater than] 8.0%). Variance-covariance structure for change from baseline was unstructured.
Measured: Baseline, Week 40
Secondary outcomes (16)
Change From Baseline in HbA1c [Superiority Analysis]
- HbA1c is the glycosylated fraction of hemoglobin A, measured to reflect average plasma glucose concentration over a prolonged period of time.
- Values represented under "Least Squares (LS) Mean" are MBE of the unconditional average treatment effect. MBE were calculated using MMRM analysis for post-baseline measures, with country, baseline by time by treatment, and strata by time by treatment in the model. Strata were defined by joint levels of HbA1c level (<=8.0%, >8.0%). Variance-covariance structure for change from baseline was unstructured.
Measured: Baseline, Week 40
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 analyzed using a logistic regression model with analysis country, treatment by baseline and treatment by strata in the model. Strata were defined by baseline HbA1c levels (<=8.0% and >8.0%). Missing Week 40 data were imputed using a multiple imputation method.
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 analyzed by logistic regression model with analysis country, treatment by baseline and treatment by strata in the model. Strata were defined by baseline HbA1c levels (<=8.0% and >8.0%). Missing Week 40 data were imputed using a multiple imputation method.
Measured: Week 40
Percent Change From Baseline in Body Weight
Values represented under "Least Squares (LS) Mean" are MBE of the unconditional average treatment effect. MBE were calculated using MMRM analysis for post-baseline measures, with country, baseline by time by treatment, and strata by time by treatment in the model. Strata were defined by joint levels of HbA1c level (<=8.0%, >8.0%). Variance-covariance structure for change from baseline was unstructured.
Measured: Baseline, Week 40
Change From Baseline in Body Weight
Values represented under "Least Squares (LS) Mean" are MBE of the unconditional average treatment effect. MBE were calculated using MMRM analysis for post-baseline measures, with country, baseline by time by treatment, and strata by time by treatment in the model. Strata were defined by joint levels of HbA1c level (<=8.0%, >8.0%). 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 MBE of the unconditional average treatment effect. MBE were calculated using MMRM analysis for post-baseline measures: log (actual measurement/baseline) = country, log (baseline) by time by treatment, and strata by time by treatment in the model. Strata were defined by joint levels of HbA1c level (<=8.0%, >8.0%). 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 MBE of the unconditional average treatment effect. MBE were calculated using MMRM analysis for post-baseline measures: log (actual measurement/baseline) = country, log (baseline) by time by treatment, and strata by time by treatment in the model. Strata were defined by joint levels of HbA1c level (<=8.0%, >8.0%). Variance-covariance structure for change from baseline was unstructured.
Measured: Baseline, Week 40
Change From Baseline in Systolic Blood Pressure (SBP)
Values represented under "Least Squares (LS) Mean" are MBE of the unconditional average treatment effect. MBE were calculated using MMRM analysis for post-baseline measures, with country, baseline by time by treatment, and strata by time by treatment in the model. Strata were defined by joint levels of HbA1c level (<=8.0%, >8.0%). Variance-covariance structure for change from baseline was unstructured.
Measured: Baseline, Week 40
Change From Baseline in Fasting Serum Glucose (FSG)
Values represented under "Least Squares (LS) Mean" are MBE of the unconditional average treatment effect. MBE were calculated using MMRM analysis for post-baseline measures, with country, baseline by time by treatment, and strata by time by treatment in the model. Strata were defined by joint levels of HbA1c level (<=8.0%, >8.0%). Variance-covariance structure for change from baseline was unstructured.
Measured: Baseline, Week 40
Percentage of Participants With ≥ 5% Body Weight Reduction
Percentage of participants with greater than or equal to (≥) 5% body weight reduction was analyzed by logistic regression model with analysis country, treatment by baseline and treatment by strata in the model. Strata were defined by baseline HbA1c levels (<=8.0% and >8.0%). Missing Week 40 data were imputed using a multiple imputation method.
Measured: Week 40
Percentage of Participants With ≥ 10% Body Weight Reduction
Percentage of participants with ≥ 10% body weight reduction was analyzed by logistic regression model with analysis country, treatment by baseline and treatment by strata in the model. Strata were defined by baseline HbA1c levels (<=8.0% and >8.0%). Missing Week 40 data were imputed using a multiple imputation method.
Measured: Week 40
Percentage of Participants With ≥ 15% Body Weight Reduction
Percentage of participants with ≥ 15% body weight reduction was analyzed by logistic regression model with analysis country, treatment by baseline and treatment by strata in the model. Strata were defined by baseline HbA1c levels (<=8.0% and >8.0%). Missing Week 40 data were imputed using a multiple imputation method.
Measured: Week 40
Change From Baseline in Diastolic Blood Pressure (DBP)
Values represented under "Least Squares (LS) Mean" are MBE of the unconditional average treatment effect. MBE were calculated using MMRM analysis for post-baseline measures, with country, baseline by time by treatment, and strata by time by treatment in the model. Strata were defined by joint levels of HbA1c level (<=8.0%, >8.0%). Variance-covariance structure for change from baseline was unstructured.
Measured: Baseline, Week 40
Percent Change From Baseline in Total Cholesterol
Values represented under "Geometric LS Mean" are MBE of the unconditional average treatment effect. MBE were calculated using MMRM analysis for post-baseline measures: log (actual measurement/baseline) = country, log (baseline) by time by treatment, and strata by time by treatment in the model. Strata were defined by joint levels of HbA1c level (<=8.0%, >8.0%). 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
Diabetes Treatment Satisfaction Questionnaire-Change Version (DTSQc): Total Score of Treatment Satisfaction
The DTSQc assesses relative change in participant satisfaction with diabetes treatment compared to previous treatment. The questionnaire consists of 8 items, of which 6 items were used to calculate the Total Score of Treatment Satisfaction, covering the following:1. satisfaction with current treatment; 2. convenience of treatment; 3. flexibility; 4. satisfaction with understanding of diabetes; 5. likelihood to recommend present treatment; and 6. satisfaction to continue present treatment. Each item is rated on a 7-point Likert scale from -3 (much less satisfied) to +3 (much more satisfied). Scores from these 6 items are summed to produce the Total Score of Treatment Satisfaction, ranging from -18 (much less satisfied) to +18 (much more satisfied). The higher the score, the greater the improvement in satisfaction with treatment; the lower the score, the greater the deterioration in satisfaction with treatment.
Measured: Week 40
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2024
- Study start10 Jan 2024
- Primary completion26 Sep 2025
- Study completion26 Sep 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
- None (open label)
- Enrolment
- 962 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
- NCT06192108
- Sponsor's protocol ID
- 18566
- Other IDs
- J2A-MC-GZGV, 2023-507206-13-00, U1111-1296-1507, 2023
- Acronym
- ACHIEVE-2
- Status last verified
- Sep 2026
- First submitted
- 21 Dec 2023
- Last updated
- 16 Oct 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
Welch M, Forst T, Jia W, Del Pino PO, Denning M, Wu WS, Li J, Liu R, Eifu M, Chen Y; ACHIEVE-2 Trial Investigators. Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 trial. Lancet. 2026 Jul 11;408(10550):125-140. doi: 10.1016/S0140-6736(26)00800-7. Epub 2026 Jun 8.
PubMed 42259339