ACHIEVE-5

CompletedPhase 3

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, 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

Lead sponsor

Eli Lilly and Company

Asset

Orforglipron

Oral · GLP-1 agonist

Listed sites

Recruiting sites

—

Enrollment

546

actual

Study population

Type 2 diabetes

Key I/E criteria

•BMI ≥23•HbA1c ≥7%

Primary endpoint

•HbA1c, change

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT06109311

Org study ID18567

Secondary ID2023-507280-18-00EU Trial Number

Secondary IDJ2A-MC-GZGWEli Lilly and Company

Secondary IDU1111-1294-2797UTN Number

Timeline

Milestones

Study first posted2023-10-31actual

Study start2023-11-10actual

Primary completion2025-09-15actual

Study completion2025-09-15actual

Last update posted2025-10-20actual

Assets

Investigational agents

Orforglipron

Study populations

Who this study enrolls

Type 2 diabetes

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•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

–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.

Exclusion criteria

•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.

Endpoints (15)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Glycemic / diabetes

Weight & body composition

Cardiometabolic biomarkers

Patient-reported / QoL

Weight & body composition

5 endpoints

Secondary/protocol endpoint

Percentage Change from Baseline in Body Weight

Time frame:Baseline, Week 40

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Body Weight

Time frame:Baseline, Week 40

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Percentage of Participants Who Achieved Weight Loss of ≥5%

Time frame:Baseline to Week 40

≥5% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Percentage of Participants Who Achieved Weight Loss of ≥10%

Time frame:Baseline to Week 40

≥10% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Percentage of Participants Who Achieved Weight Loss of ≥15% from Baseline

Time frame:Baseline to Week 40

≥15% weight-loss responders

threshold achievement, improvement

Glycemic / diabetes

6 endpoints

Primary/protocol endpoint

Orforglipron Dose 1, 2: Change from Baseline in Hemoglobin A1c (HbA1c)

Time frame:Baseline, Week 40

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Orforglipron Dose 3: Change from Baseline in HbA1c

Time frame:Baseline, Week 40

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Percentage of Participants Who Achieved HbA1c <7.0% (53 millimoles per mole (mmol/mol))

Time frame:Baseline to Week 40

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Percentage of Participants Who Achieved HbA1c ≤6.5% (48 mmol/mol)

Time frame:Baseline to Week 40

HbA1c <6.5% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change from Baseline in Fasting Serum Glucose

Time frame:Baseline, Week 40

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change from Baseline in Daily Insulin Glargine Dose

Time frame:Baseline, Week 40

change from baseline, improvement

Cardiometabolic biomarkers

3 endpoints

Secondary/protocol endpoint

Percentage Change from Baseline in non-HDL (non-high-density lipoprotein) Cholesterol

Time frame:Baseline, Week 40

Non-HDL cholesterol, change

percent change from baseline, improvement

Secondary/protocol endpoint

Percentage Change from Baseline in Triglycerides

Time frame:Baseline, Week 40

Triglycerides, change

percent change from baseline, improvement

LOINC 2571-8

Secondary/protocol endpoint

Change from Baseline in Systolic Blood Pressure

Time frame:Baseline, Week 40

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Patient-reported / QoL

1 endpoint

Secondary/protocol endpoint

Change from Baseline in Short Form 36-Version 2 (SF-36v2) Acute Form Domain and Summary Scores

Time frame:Baseline, Week 40

SF-36 total

change from baseline, improvement

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

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 Jun 7. doi: 10.1001/jama.2026.9512. Online ahead of print.
PMID42251769via clinicaltrials gov reference derived

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.