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Type 2 DiabetesPhase 3ACHIEVE-5NCT06109311

A Study of Orforglipron (LY3502970) in Participants With Type 2 Diabetes and Inadequate Glycemic Control With Insulin Glargine, With or Without Metformin and/or SGLT-2 Inhibitor

A Phase 3 study testing Orforglipron in people with Type 2 Diabetes, run by Eli Lilly and Company at 70 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The main purpose of this study is to determine the safety and efficacy of orforglipron. Participants will have Type 2 Diabetes (T2D) and have inadequate glycemic control with insulin glargine with or without metformin and/or SGLT-2 (sodium-glucose cotransporter-2) inhibitor. 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
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
546 participants
Where
70 sitesin 6 countries
Study dates
10 Nov 2023to 15 Sep 2025
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 (T2D)
  • Have HbA1c ≥7.0% [53 mmol/mol] to ≤10.5% [91 mmol/mol]
  • Have been treated with stable doses of the same formulation of the following for ≥90 days prior to screening visit 1 and have maintained the same doses through randomization:
  • insulin glargine U-100 (100 U/mL) ≥0.25 U/kg/QD (units per kilogram per day) or ≥20 U/QD alone, or
  • insulin glargine U-100 (100 U/mL) ≥0.25 U/kg/QD or ≥20 U/QD in combination with
  • metformin, or
Show all 10Show fewer
  • SGLT-2 inhibitor, or
  • both metformin and SGLT-2 inhibitor.
  • Are of stable body weight (±5%) for at least 90 days prior to screening visit 1 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 kg/m^2 at baseline.

Who cannot join

  • Have New York Heart Association functional classification III-IV congestive heart failure.
  • Have had any of the following cardiovascular conditions within 60 days prior to baseline.
  • acute myocardial infarction
  • cerebrovascular accident (stroke), or
  • hospitalization for congestive heart failure.
  • Have acute or chronic hepatitis, including a history of autoimmune hepatitis, signs or symptoms of any other liver disease other than nonalcoholic fatty liver disease
  • Have had chronic or acute pancreatitis any time.

Trial locations and contacts

70 sites in 6 countries.

70 sites in 6 countries

United States25 sites

  • Bingham Memorial Hospital

    Blackfoot, Idaho, 83221

  • St. Luke's Humphreys Diabetes Center: Boise

    Boise, Idaho, 83702

  • Care Access - Brandon

    Brandon, Florida, 33510

  • SanRo Clinical Research Group

    Bryant, Arkansas, 72022

  • MD First Research - Chandler

    Chandler, Arizona, 85286

  • Velocity Clinical Research, Mt. Auburn

    Cincinnati, Ohio, 45219

  • Orita Clinical Research

    Decatur, Georgia, 30034

  • Velocity Clinical Research, Gardena

    Gardena, California, 90247

  • CMR of Greater New Haven, LLC

    Hamden, Connecticut, 06517

  • Encore Medical Research

    Hollywood, Florida, 33024

  • The Research Group of Lexington

    Lexington, Kentucky, 40503

  • Loma Linda University Health System

    Loma Linda, California, 92350

  • Velocity Clinical Research, Medford

    Medford, Oregon, 97504

  • Lifedoc Research - Lenox Park Drive

    Memphis, Tennessee, 38115

  • Tristar Clinical Investigations

    Philadelphia, Pennsylvania, 19114

  • Phoenix Clinical LLC

    Phoenix, Arizona, 85014

  • Western University of Health Sciences

    Pomona, California, 91766

  • Frontier Clinical Research, LLC

    Scottdale, Pennsylvania, 15683

  • Consano Clinical Research, LLC

    Shavano Park, Texas, 78231

  • Clinvest Headlands Llc

    Springfield, Missouri, 65807

  • Richmond University Medical Center

    Staten Island, New York, 10310

  • Med Partners, Inc. dba Premiere Medical Center of Burbank, Inc.

    Toluca Lake, California, 91602

  • Cotton O'Neil Diabetes & Endocrinology

    Topeka, Kansas, 66606

  • Texas Valley Clinical Research

    Weslaco, Texas, 78596

  • Encore Medical Research - Weston

    Weston, Florida, 33331

Other trials in United States

Japan14 sites

  • 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

  • Matoba Internal Medicine Clinic

    Ebina, Kanagawa, 243-0432

  • Takai Internal Medicine Clinic

    Kamakura-shi, Kanagawa, 247-0056

  • Shiraiwa Medical Clinic

    Kashihara, Osaka, 582-0005

  • Jinnouchi Hospital

    Kumamoto, 862-0976

  • Tokuyama Clinic

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

  • MinamiAkatsukaClinic

    Mito, Ibaraki, 311-4153

  • Abe Clinic

    Ōita, 870-0039

  • Medical Corporation Sato Medical clinic

    Ootaku, Tokyo, 143-0015

  • Kansai Electric Power Hospital

    Osaka, 553-0003

  • Tama Center Clinic Mirai

    Tama, Tokyo, 206-0633

Other trials in Japan

China10 sites

  • Beijing Hospital

    Beijing, Beijing Municipality, 100051

  • Chongqing General Hospital

    Chongqing, Chongqing Municipality, 401147

  • The Second People's Hospital of Hefei

    Hefei, Anhui, 230011

  • Jinan Central Hospital

    Jinan, Shandong, 250013

  • The First Affiliated Hospital of Henan University of Science &Technology

    Luoyang Shi, Henan, 471003

  • The Second Affiliated Hospital of Nanjing Medical University

    Nanjing, Jiangsu, 210011

  • Nanjing First Hospital

    Nanjing, Jiangsu, 210012

  • 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

Other trials in China

Romania10 sites

  • CMI DNBM Dr. Pop Lavinia

    Baia Mare, Maramureş, 430222

  • C.M.D.T.A. Neomed

    Brasov, Brașov County, 500283

  • Geea Medical Easy Diet

    Bucharest, Bucharest, 010627

  • Centrul Medical NutriLife

    Bucharest, Bucharest, 013764

  • Centrul Medical Endocrinologie si Diabet Dr. Paveliu

    Bucharest, Bucharest, 50538

  • Milena Sante

    Galați, 800001

  • Diamed Obesity

    Galați, 800291

  • Diabdana

    Oradea, Bihor County, 410147

  • Clinica Korall

    Satu Mare, 440055

  • SC Dentosim Queen SRL - Centrul Medical Diamed

    Târgu Mureş, Mureș County, 540098

Other trials in Romania

Brazil9 sites

  • L2IP - Instituto de Pesquisas Clínicas

    Brasília, Federal District, 70200730

  • Centro de Pesquisa Sao Lucas

    Campinas, São Paulo, 13060-803

  • Quanta Diagnóstico e Terapia

    Curitiba, Paraná, 80040-110

  • Insight Centro de Pesquisas

    Porto Alegre, Rio Grande do Sul, 90560-003

  • IBPClin - Instituto Brasil de Pesquisa Clínica

    Rio de Janeiro, 20241-180

  • Centro Multidisciplinar de Estudos Clinicos

    São Bernardo do Campo, São Paulo, 09715-090

  • ISPEM - Instituto São José dos Campos em Pesquisas Médicas

    São José dos Campos, São Paulo, 12243-280

  • CPQuali Pesquisa Clínica

    São Paulo, 01228-000

  • CEDOES

    Vitória, Espírito Santo, 29055450

Other trials in Brazil

Puerto Rico2 sites

  • Centro de Endocrinologia y Nutricion

    Caguas, 00725

  • FDI Clinical Research

    San Juan, 00927

Other trials in Puerto Rico

About this study

Official title: A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once Daily Oral Orforglipron Compared With Placebo in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Insulin Glargine, With or Without Metformin and/or SGLT-2 Inhibitor

The main purpose of this study is to determine the safety and efficacy of orforglipron. Participants will have Type 2 Diabetes (T2D) and have inadequate glycemic control with insulin glargine with or without metformin and/or SGLT-2 (sodium-glucose cotransporter-2) inhibitor. The study will last about 46 weeks and may include up to 20 visits.

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 groups in NCT06109311
Study groupRoleWhat they receive
PlaceboPlacebo comparatorParticipants received matching placebo administered orally once daily (QD) and insulin glargine therapy (100 Units per milliliter (U/mL)) administered subcutaneously (SC) QD, over a period of 40 weeks.
Receives: Drug: Placebo
3 mg Orforglipron QDExperimentalParticipants received oral orforglipron, initiated at 1 milligram (mg) and increased every 4 weeks until reaching to a maintenance dose of 3 mg QD and insulin glargine therapy 100 U/mL administered SC QD, over a period of 40 weeks.
Receives: Drug: Orforglipron
12 mg Orforglipron QDExperimentalParticipants received oral orforglipron, initiated at 1 mg and increasing every 4 weeks until reaching to a maintenance dose of 12 mg QD and insulin glargine therapy 100 U/mL administered SC QD, over a period of 40 weeks.
Receives: Drug: Orforglipron
36 mg Orforglipron QDExperimentalParticipants received oral orforglipron, initiated at 1 mg and increasing every 4 weeks until reaching to a maintenance dose of 36 mg QD and insulin glargine therapy 100 U/mL administered SC QD, over a period of 40 weeks.
Receives: Drug: Orforglipron

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in Hemoglobin A1c (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 SGLT-2 inhibitor use at randomization [Yes or No]. Variance-covariance structure for change from baseline was unstructured.

    Measured: Baseline, Week 40

Secondary outcomes (13)

  1. 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 SGLT-2 inhibitor use at randomization [Yes or No].

    Measured: Week 40

  2. 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 SGLT-2 inhibitor use at randomization [Yes or No].

    Measured: Week 40

  3. 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 SGLT-2 inhibitor use at randomization [Yes or No]. Variance-covariance structure for change from baseline was unstructured.

    Measured: Baseline, Week 40

  4. 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 SGLT-2 inhibitor use at randomization [Yes or No]. Variance-covariance structure for change from baseline was unstructured.

    Measured: Baseline, Week 40

  5. Change From Baseline in Body Weight (kg)

    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 SGLT-2 inhibitor use at randomization [Yes or No]. Variance-covariance structure for change from baseline was unstructured.

    Measured: Baseline, Week 40

  6. Percent Change From Baseline in Non-HDL (Non-high-density Lipoprotein) Cholesterol

    Values represented under "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 were defined by joint levels of baseline HbA1c (≤8.0%, >8.0%) and SGLT-2 inhibitor use at randomization [Yes or No]. Variance-covariance structure for change from baseline was unstructured.

    Measured: Baseline, Week 40

  7. Percent Change From Baseline in Triglycerides

    Values represented under "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 were defined by joint levels of baseline HbA1c (≤8.0%, >8.0%) and SGLT-2 inhibitor use at randomization [Yes or No]. Variance-covariance structure for change from baseline was unstructured.

    Measured: Baseline, Week 40

  8. Change From Baseline in Systolic Blood Pressure (mmHg)

    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 SGLT-2 inhibitor use at randomization [Yes or No]. Variance-covariance structure for change from baseline was unstructured.

    Measured: Baseline, Week 40

  9. Change From Baseline in Daily Insulin Glargine Dose (IU/Day)

    Values represented under "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 were defined by joint levels of baseline HbA1c (≤8.0%, >8.0%) and SGLT-2 inhibitor use at randomization [Yes or No]. Variance-covariance structure for change from baseline was unstructured.

    Measured: Baseline, Week 40

  10. 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 SGLT-2 inhibitor use at randomization [Yes or No].

    Measured: Week 40

  11. Percentage of Participants With Greater Than or Equal to (≥) 10% Body Weight Reduction

    Percentage of participants with ≥10% 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 SGLT-2 inhibitor use at randomization [Yes or No].

    Measured: Week 40

  12. Percentage of Participants With Greater Than or Equal to (≥) 15% Body Weight Reduction

    Percentage of participants with ≥15% 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 SGLT-2 inhibitor use at randomization [Yes or No].

    Measured: Week 40

  13. 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.

  1. First posted31 Oct 2023
  2. Study start10 Nov 2023
  3. Primary completion15 Sep 2025
  4. Study completion15 Sep 2025

Resources

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
546 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06109311
Sponsor's protocol ID
18567
Other IDs
J2A-MC-GZGW, U1111-1294-2797, 2023-507280-18-00, 2023
Acronym
ACHIEVE-5
Status last verified
Sep 2026
First submitted
26 Oct 2023
Last updated
1 Oct 2026
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

  • Giorgino F, D'Souza S, Ludwig L, Kiyosue A, Ibriga H, Rha H, Denning M, Wu WS, Fernandez Lando L, Tobian J. Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial. JAMA. 2026 Aug 4;336(5):389-399. doi: 10.1001/jama.2026.9512.

    PubMed 42251769

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Orforglipron in people with Type 2 Diabetes, run by Eli Lilly and Company at 70 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 70 sites in United States, Japan, China, Romania, Brazil and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Hemoglobin A1c (HbA1c) (time frame: Baseline, Week 40). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06109311, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2026.

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