A Long-term Safety Study of Orforglipron (LY3502970) in Participants With Type 2 Diabetes (ACHIEVE-J)

A Phase 3, Long-term Safety Study of LY3502970 in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone or in Combination With Oral Antihyperglycemic Medications (ACHIEVE-J)

The purpose of this study is to determine the long-term safety of the study intervention orforglipron as a monotherapy or in combination with oral antihyperglycemic medication.

This study includes 3 periods as follows:

• screening and lead-in period: up to 4 weeks
• treatment period: 52 weeks, including 20 weeks of dose escalation, and
• safety follow-up period: 2 weeks.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 401
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 814-0153
    • Tashiro Endocrinology Clinic
  • Kumamoto, Japan, 862-0976
    • Jinnouchi Hospital
  • Kumamoto, Japan, 860-0863
    • Morinaga Ueno Clinic
  • Miyazaki, Japan, 880-0034
    • Heiwadai Hospital
  • Osaka, Japan, 553-0003
    • Kansai Electric Power Hospital
  • Ōita, Japan, 870-0039
    • Abe Clinic
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 456-0058
      • Nakayama Clinic
  • Chiba
    • Kashiwa, Chiba, Japan, 277-0825
      • Kashiwa City Hospital
    • Kashiwa, Chiba, Japan, 277-0084
      • Shinkashiwa Clinic
    • Mihama-ku,Chiba City, Chiba, Japan, 261-0004
      • Tokuyama Clinic
  • Ehime
    • Matsuyama, Ehime, Japan, 790-0034
      • Mikannohana Clinic, Diabetes, Endocrinology and Metabolism
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan, 805-8508
      • Steel Memorial Yawata Hospital
  • Hokkaido
    • Chitose, Hokkaido, Japan, 066-0032
      • Hasegawa Medical Clinic
    • Sapporo, Hokkaido, Japan, 060-0001
      • Odori Diabetes
  • Hyōgo
    • Kobe, Hyōgo, Japan, 651-2135
      • Matsuda Clinic
  • Ibaraki
    • Mito, Ibaraki, Japan, 310-0826
      • Nakamoto Internal Medicine Clinic
    • Mito, Ibaraki, Japan, 311-4153
      • MinamiAkatsukaClinic
    • Naka, Ibaraki, Japan, 311-0113
      • Nakakinen clinic
    • Naka, Ibaraki, Japan, 311-0133
      • Nishiyamadou Keiwa Hospital
    • Tsuchiura, Ibaraki, Japan, 300-0047
      • Taya Clinic Koueikai Medical Corporation
  • Kanagawa
    • Kamakura, Kanagawa, Japan, 247-0055
      • Shonan Takai Clinic
    • Kamakura-shi, Kanagawa, Japan, 247-0056
      • Takai Internal Medicine Clinic
    • Yamato-shi, Kanagawa, Japan, 242-0004
      • Medical Corporation Yuga Tsuruma Kaneshiro Diabetes Clinic
    • Yokohama, Kanagawa, Japan, 232-0064
      • Yokohama Minoru Clinic
  • Mie-ken
    • Yokkaichi, Mie-ken, Japan, 510-0829
      • Yokkaichi Diabetes Clinic
  • Nagano
    • Matsumoto, Nagano, Japan, 399-0036
      • Gibo Hepatology Clinic
  • Osaka
    • Kashihara, Osaka, Japan, 582-0005
      • Shiraiwa Medical Clinic
    • Osaka, Osaka, Japan, 538-0044
      • Kitada Clinic
    • Suita-shi, Osaka, Japan, 565-0853
      • Medical Corporation Heishinkai OCROM Clinic
  • Saitama
    • Kawaguchi, Saitama, Japan, 332-0015
      • OHAMA Diabetes Clinic
    • Sōka, Saitama, Japan, 340-0015
      • Sugiura Internal Medicine Clinic
  • Tokyo
    • Adachi-ku, Tokyo, Japan, 120-0011
      • Seiwa Clinic
    • 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 for Adult Disease, Asahi Life Foundation
    • Hachioji-shi, Tokyo, Japan, 192-0083
      • Hachioji Diabetes Clinic
    • Mitaka, Tokyo, Japan, 181-0013
      • Kanno Naika
    • Shinjuku-ku, Tokyo, Japan, 160-0008
      • Heishinkai Medical Group ToCROM Clinic
  • Yamaguchi
    • Ube, Yamaguchi, Japan, 755-0047
      • Medical Corporation Tao Internal Medicine Clinic
    • Ube, Yamaguchi, Japan, 755-0049
      • Fujii Clinic

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Have Type 2 Diabetes (T2D)
• Have HbA1c ≥7.0% (≥53 mmol/mol) to ≤10.5% (≤91 mmol/mol) as determined by the central laboratory at screening.
• 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 BMI ≥23.0 kilogram/square meter (kg/m²) at screening.

Exclusion Criteria:

• Have Type 1 Diabetes (T1D).
• Have a history of severe hypoglycemia or hypoglycemia unawareness within the last 6 months prior to screening, or between screening and randomization.
• Have New York Heart Association functional classification IV congestive heart failure.

• Have had any of the following cardiovascular (CV) conditions within 60 days prior to screening, or between screening and randomization.

  • acute myocardial infarction
  • cerebrovascular accident (stroke), or
  • hospitalization for congestive heart failure
• Have acute or chronic hepatitis and pancreatitis

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 3 mg Orforglipron; Participants received once-daily oral orforglipron for 52 weeks. Treatment began with a 1-mg loading dose for the first 4 weeks, followed by the maintenance dose of 3 mg for the remainder of the duration.	Drug: Orforglipron; Administered orally; Other Names: LY3502970
Experimental: 12 mg Orforglipron; Participants received once-daily oral orforglipron for 52 weeks. Treatment began with a 1-mg loading dose for the first 4 weeks, followed by dose escalations every 4 weeks to reach the maintenance dose of 12 mg at week 12, which was then continued for the remainder of the duration.	Drug: Orforglipron; Administered orally; Other Names: LY3502970
Experimental: 36 mg Orforglipron; Participants received once-daily oral orforglipron for 52 weeks. Treatment began with a 1-mg loading dose for the first 4 weeks, followed by dose escalations every 4 weeks to reach the maintenance dose of 36 mg at week 20, which was then continued for the remainder of the duration.	Drug: Orforglipron; Administered orally; Other Names: LY3502970

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	A TEAE was defined as any adverse event that began on or after the first dose of study drug or began before the first dose of study drug and worsened on or after the first dose of study drug.	Baseline to Week 54

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hemoglobin A1c (HbA1c)	HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time.	Baseline, Week 52
Percentage of Participants Who Achieved HbA1c <7.0%	HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. The reported values represent model-based estimates. The Mean (SE) is an estimated values from a logistic regression using imputed data by multiple imputation, with percentages derived by combining proportion of participants achieving target in imputed data sets using Rubin's rule.	Week 52
Percentage of Participants Who Achieved HbA1c ≤6.5%	HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. The reported values represent model-based estimates. The Mean (SE) is an estimated values from a logistic regression using imputed data by multiple imputation, with percentages derived by combining proportion of participants achieving target in imputed data sets using Rubin's rule.	Week 52
Percentage of Participants Who Achieved HbA1c <5.7%	HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. The reported values represent model-based estimates. The Mean (SE) is an estimated values from a logistic regression using imputed data by multiple imputation, with percentages derived by combining proportion of participants achieving target in imputed data sets using Rubin's rule.	Week 52
Change From Baseline in Fasting Serum Glucose		Baseline, Week 52
Change From Baseline in Body Weight		Baseline, Week 52
Percentage of Participants Who Achieved Weight Loss of ≥5% From Baseline	The reported values represent model-based estimates. The Mean (SE) is an estimated values from a logistic regression using imputed data by multiple imputation, with percentages derived by combining proportion of participants achieving target in imputed data sets using Rubin's rule.	Week 52
Percentage of Participants Who Achieved Weight Loss of ≥10% From Baseline	The reported values represent model-based estimates. The Mean (SE) is an estimated values from a logistic regression using imputed data by multiple imputation, with percentages derived by combining proportion of participants achieving target in imputed data sets using Rubin's rule.	Week 52
Percentage of Participants Who Achieved Weight Loss of ≥15% From Baseline	The reported values represent model-based estimates. The Mean (SE) is an estimated values from a logistic regression using imputed data by multiple imputation, with percentages derived by combining proportion of participants achieving target in imputed data sets using Rubin's rule.	Week 52
Change From Baseline in Waist Circumference		Baseline, Week 52
Change From Baseline in Body Mass Index (BMI)		Baseline, Week 52
Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG)	SMBG is measured using a glucometer. The SMBG profiles will consist of the following 7-point measurements obtained on a single day: before 3 main meals,; approximately 2 hours after 3 main meals, and; at bedtime Daily average glucose was calculated as the mean of 7 time point specific averages obtained from up to 2 non-consecutive SMBG profiles within week 52.	Baseline, Week 52

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 Phase 3, Long-term Safety Study of LY3502970 in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone or in Combination With Oral Antihyperglycemic Medications (ACHIEVE-J)

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2023
• Primary Completion (Actual): June 5, 2025
• Study Completion (Actual): June 5, 2025

Study Registration Dates

• First Submitted: August 21, 2023
• First Submitted That Met QC Criteria: August 21, 2023
• First Posted (Actual): August 24, 2023

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 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: 18745; J2A-JE-GZPE (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient 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
• product manufactured in and exported from the U.S.: Yes