A Study of Orforglipron (LY3502970) Compared With Dapagliflozin in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin (ACHIEVE-2)

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 962
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230011
      • The Second People's Hospital of Hefei
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • The Fourth Affiliated Hospital of Harbin Medical University
  • Henan
    • Nanyang, Henan, China, 473007
      • The First Affiliated Hospital of Nanyang Medical College
    • 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
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University
    • Zhenjiang, Jiangsu, China, 212000
      • Affiliated Hospital of Jiangsu University
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Shanghai Sixth People's Hospital
  • Yunnan
    • Kunming, Yunnan, China, 650032
      • First Affiliated Hospital of Kunming Medical University
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325000
      • The First Affiliated Hospital of Wenzhou Medical University
• Germany
  • Hamburg, Germany, 21109
    • Diabetes Zentrum Wilhelmsburg
  • Baden-Wurttemberg
    • Mannheim, Baden-Wurttemberg, Germany, 68167
      • CRS Clinical Research Services Mannheim
  • Lower Saxony
    • Lingen, Lower Saxony, Germany, 49808
      • Diabetologische Schwerpunktpraxis Dr. Staudenmeyer & Dr. Schiwietz
  • North Rhine-Westphalia
    • Bochum, North Rhine-Westphalia, Germany, 44869
      • Diabetes- und Stoffwechselpraxis Bochum
    • Cologne, North Rhine-Westphalia, Germany, 51069
      • Zentrum fur klinische Forschung - Köln
    • Essen, North Rhine-Westphalia, Germany, 45355
      • Medizentrum Essen Borbeck
    • Essen, North Rhine-Westphalia, Germany, 45136
      • InnoDiab Forschung GmbH
    • Münster, North Rhine-Westphalia, Germany, 48145
      • Institut für Diabetesforschung GmbH Münster
  • Saarland
    • Rehlingen, Saarland, Germany, 66780
      • Praxis Dr. Veronika Wenzl-Bauer
    • Saint Ingbert, Saarland, Germany, 66386
      • Zentrum für klinische Studien
  • Schleswig-Holstein
    • Oldenburg in Holstein, Schleswig-Holstein, Germany, 23758
      • RED-Institut GmbH
• Mexico
  • Aguascalientes, Mexico, 20230
    • Fundación Cardiovascular de Aguascalientes A.C.
  • Durango, Mexico, 34000
    • Lahoja. Asociacion Para La Investigacion Y La Farmacovigilancia
  • Hidalgo
    • Pachuca, Hidalgo, Mexico, 42000
      • Grupo Ollin Care
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44600
      • Instituto Jalisciense de Investigacion en Diabetes y Obesidad
  • Mexico City
    • Cuauhtémoc, Ciudad de México, Mexico City, Mexico, 06100
      • Cryptex Investigación Clínica S.A. de C.V.
    • Mexico City, Mexico City, Mexico, 14050
      • ProcliniQ Investigación Clínica SA de CV
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62250
      • Instituto de Diabetes, Obesidad y Nutricion
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64610
      • Clínica García Flores SC
    • Monterrey, Nuevo León, Mexico, 64060
      • Cardiolink Clin Trials
    • San Nicolás de los Garza, Nuevo León, Mexico, 66450
      • Servicios Integrales Nova de Monterrey S.A. de C.V.
  • Sinaloa
    • Culiacán, Sinaloa, Mexico, 80230
      • Centro para el Desarrollo de la Medicina y de Asistencia Médica Especializada S.C.
  • Veracruz
    • Xalapa, Veracruz, Mexico, 91193
      • Hospital Angeles Xalapa
    • Xalapa, Veracruz, Mexico, 91193
      • Consultorio de Medicina Especilizada del Sector Privado
• Poland
  • Kuyavian-Pomeranian Voivodeship
    • Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland, 85-231
      • NZOZ Centrum Medyczne KERmed
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 31-261
      • Medyczne Centrum Diabetologiczno Endokrynologiczno Metaboliczne DIAB-ENDO-MET
  • Lower Silesian Voivodeship
    • Wroclaw, Lower Silesian Voivodeship, Poland, 50-162
      • Centrum Badań Klinicznych Piotr Napora lekarze sp.p.
  • Lublin Voivodeship
    • Lublin, Lublin Voivodeship, Poland, 20-011
      • Clinical Best Solutions
    • Lublin, Lublin Voivodeship, Poland, 20-044
      • CenterMed Lublin NZOZ
    • Lublin, Lublin Voivodeship, Poland, 20-718
      • Ekamed
  • Masovian Voivodeship
    • Radom, Masovian Voivodeship, Poland, 26-600
      • Centrum Medyczne "Diabetika"
  • Podlaskie Voivodeship
    • Bialystok, Podlaskie Voivodeship, Poland, 15-351
      • Zdrowie Osteo-Medic
    • Bialystok, Podlaskie Voivodeship, Poland, 15-375
      • Specderm Poznanska
  • Silesian Voivodeship
    • Zabrze, Silesian Voivodeship, Poland, 41-800
      • Samodzielny Publiczny Szpital Kliniczny nr 1 SUM
  • Łódź Voivodeship
    • Lodz, Łódź Voivodeship, Poland, 90-338
      • Centrum Terapii Wspolczesnej J. M. Jasnorzewska Spolka Komandytowo-Akcyjna
• Taiwan
  • Kaohsiung City, Taiwan, 81362
    • Kaohsiung Veterans General Hospital
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • New Taipei City, Taiwan, 24352
    • Fu Jen Catholic University Hospital
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital
  • Tainan City, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Kaohsiung
    • Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan, 83301
      • Chang Gung Memorial Hospital at Kaohsiung
• United States
  • California
    • Canoga Park, California, United States, 91304
      • Alliance Research Institute - Canoga Park
    • Long Beach, California, United States, 90815
      • Ark Clinical Research
    • Los Alamitos, California, United States, 90720
      • Collaborative Neuroscience Research, LLC
    • Santa Ana, California, United States, 92706
      • Wolverine Clinical Trials
  • Connecticut
    • Hamden, Connecticut, United States, 06517
      • CMR of Greater New Haven, LLC
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • Institute of Endocrinology Diabetes, Health & Hormone
  • Idaho
    • Rexburg, Idaho, United States, 83440
      • Elite Clinical Trials
  • Illinois
    • Lombard, Illinois, United States, 60148
      • Accellacare - DuPage
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research
  • Montana
    • Billings, Montana, United States, 59101
      • St. Vincent Healthcare
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials, Inc.
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Accellacare - Winston-Salem
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Alliance for Multispecialty Research, LLC
    • Tulsa, Oklahoma, United States, 74137
      • Essential Medical Research
  • South Carolina
    • Mt. Pleasant, South Carolina, United States, 29464
      • Accellacare - Mt Pleasant
  • Tennessee
    • Jefferson City, Tennessee, United States, 37760
      • Accellacare, US Inc., d/b/a Accellacare of Knoxville
  • Texas
    • Dallas, Texas, United States, 75230
      • Velocity Clinical Research, Dallas
    • Houston, Texas, United States, 77040
      • Juno Research
    • Shavano Park, Texas, United States, 78231
      • Consano Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

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
Experimental: Orforglipron Dose 3; Participants will receive orforglipron orally.	Drug: Orforglipron; Administered orally; Other Names: LY3502970
Active Comparator: Dapagliflozin; Participants will receive dapagliflozin orally.	Drug: Dapagliflozin; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in Hemoglobin A1c: (HbA1c)	Baseline, Week 40

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in Fasting Serum Glucose	Baseline, Week 40
Change from Baseline in Body Weight	Baseline, Week 40
Percentage Change from Baseline in Body Weight	Baseline, Week 40
Change from Baseline in Systolic Blood Pressure (SBP)	Baseline, Week 40
Percentage Change from Baseline in Triglycerides	Baseline, Week 40
Change from Baseline in HbA1c	Baseline, Week 40
Percentage of Participants Who Achieved HbA1c <7.0% (53 millimole/mole(mmol/mol))	Week 40
Percentage of Participants Who Achieved HbA1c ≤6.5% (48 mmol/mol)	Week 40
Percentage Change from Baseline in Non-High-Density Lipoprotein (non-HDL)-Cholesterol	Baseline, Week 40
Percentage of Participants Who Achieved Weight Loss of ≥5% from Baseline	Baseline to Week 40
Percentage of Participants Who Achieved Weight Loss of ≥10% from baseline	Baseline to Week 40
Percentage of Participants Who Achieved Weight Loss of ≥15% from baseline	Baseline to Week 40
Change from Baseline in Diastolic Blood Pressure (DBP)	Baseline, Week 40
Percentage Change from Baseline in Total Cholesterol	Baseline, Week 40
Change from Baseline in Short Form 36 Version 2 (SF-36-v2) Acute Form Domain Summary Scores	Baseline, Week 40
Change from Baseline in Diabetes Treatment Satisfaction Questionnaire-Change (DTSQc) 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

Helpful Links

• A Study of Orforglipron (LY3502970) Compared With Dapagliflozin in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin (ACHIEVE-2)

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2024
• Primary Completion (Actual): September 26, 2025
• Study Completion (Actual): September 26, 2025

Study Registration Dates

• First Submitted: December 21, 2023
• First Submitted That Met QC Criteria: December 21, 2023
• First Posted (Actual): January 5, 2024

Study Record Updates

• Last Update Posted (Estimated): October 20, 2025
• Last Update Submitted That Met QC Criteria: October 16, 2025
• Last Verified: October 1, 2025

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; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; orforglipron; dapagliflozin
• Other Study ID Numbers: 18566; J2A-MC-GZGV (Other Identifier: Eli Lilly and Company); 2023-507206-13-00 (Other Identifier: EU Trial Number); U1111-1296-1507 (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