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ACHIEVE-1

CompletedPhase 3Results posted

A Study of Orforglipron (LY3502970) in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone

A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once Daily Oral LY3502970 Compared With Placebo in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone

Lead sponsor

Eli Lilly and Company

Asset

Orforglipron

Oral · GLP-1 agonist

Listed sites

Recruiting sites

—

Enrollment

559

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 IDNCT05971940

Org study ID18564

Secondary IDJ2A-MC-GZGTEli Lilly and Company

Secondary IDU1111-1290-5157UTN Number

Timeline

Milestones

Study first posted2023-08-02actual

Study start2023-08-09actual

Primary completion2025-04-03actual

Study completion2025-04-03actual

Last update posted2026-04-22actual

Results first posted2026-04-22actual

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

•Have HbA1c ≥7.0% (53 mmol/mol) to ≤9.5% (80 mmol/mol) despite diet and exercise treatment, as determined by the central laboratory at screening.

•Are naïve to insulin therapy except for gestational diabetes or ≤14 days use for acute treatment and have not used any oral or injectable antihyperglycemic medications during the 90 days preceding screening or between screening and randomization.

•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 body mass index (BMI) ≥23.0 kilogram/square meter (kg/m²) at screening.

Exclusion criteria

•Have Type 1 Diabetes

•Have a history of ketoacidosis or hyperosmolar state or coma within the last 6 months prior to screening, or between screening and randomization.

•Currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema

•Have New York Heart Association functional classification IV congestive heart failure.

•Have acute or chronic pancreatitis

Endpoints (24)

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

6 endpoints

Secondary/registry result

Percent Change From Baseline in Body Weight

Time frame:Baseline, Week 40

Body weight, % change

percent change from baseline, improvement

Posted result

Group	Value (least_squares_mean), percent change	95% CI
Placebo	-1.6	—
3 mg Orforglipron	-4.7	—
12 mg Orforglipron	-6.1	—
36 mg Orforglipron	-7.9	—

LS Mean Difference (Net)-3.195% CI-4.4 – -1.8p<.001Mixed Models Analysis

LS Mean Difference (Net)-4.595% CI-5.9 – -3.1p<.001Mixed Models Analysis

LS Mean Difference (Net)-6.395% CI-7.7 – -4.8p<.001Mixed Models Analysis

Secondary/registry result

Change From Baseline in Body Weight

Time frame:Baseline, Week 40

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), kilogram (kg)	95% CI
Placebo	-1.3	—
3 mg Orforglipron	-4.4	—
12 mg Orforglipron	-5.5	—
36 mg Orforglipron	-7.3	—

LS Mean Difference (Net)-3.195% CI-4.2 – -2.0p<.001Mixed Models Analysis

LS Mean Difference (Net)-4.295% CI-5.5 – -3.0p<.001Mixed Models Analysis

LS Mean Difference (Net)-6.095% CI-7.3 – -4.6p<.001Mixed Models Analysis

Secondary/registry result

Percentage of Participants With Greater Than or Equal to (≥) 5% Body Weight Reduction

Time frame:Week 40

≥5% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (number), percentage of participants	95% CI
Placebo	14.58	—
3 mg Orforglipron	47.06	—
12 mg Orforglipron	58.56	—
36 mg Orforglipron	66.39	—

Risk Difference (RD)25.3695% CI14.25 – 36.47p<.001Regression, Logistic

Risk Difference (RD)37.2895% CI26.05 – 48.50p<.001Regression, Logistic

Risk Difference (RD)44.8095% CI33.54 – 56.06p<.001Regression, Logistic

Secondary/protocol endpoint

Percent 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 With Greater Than or Equal to (≥) 5% Body Weight Reduction

Time frame:Week 40

≥5% weight-loss responders

threshold achievement, improvement

Glycemic / diabetes

10 endpoints

Primary/registry result

Change From Baseline in HbA1c

Time frame:Baseline, Week 40

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (least_squares_mean), percentage of HbA1c	95% CI
Placebo	-0.15	—
3 mg Orforglipron	-1.26	—
12 mg Orforglipron	-1.59	—
36 mg Orforglipron	-1.45	—

Least Square (LS) Mean Difference (Net)-1.1295% CI-1.43 – -0.80p<.001Mixed Models Analysis

LS Mean Difference (Net)-1.4495% CI-1.72 – -1.16p<.001Mixed Models Analysis

LS Mean Difference (Net)-1.3095% CI-1.61 – -1.00p<.001Mixed Models Analysis

Primary/protocol endpoint

Change From Baseline in HbA1c

Time frame:Baseline, Week 40

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/registry result

Percentage of Participants With an HbA1c Target Value of < 7.0% (53 mmol/Mol)

Time frame:Week 40

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (number), percentage of participants	95% CI
Placebo	37.11	—
3 mg Orforglipron	78.15	—
12 mg Orforglipron	81.25	—
36 mg Orforglipron	78.99	—

Risk Difference (RD)44.9095% CI34.41 – 55.39p<.001Regression, Logistic

Risk Difference (RD)48.2295% CI37.50 – 58.93p<.001Regression, Logistic

Risk Difference (RD)46.9495% CI36.61 – 57.28p<.001Regression, Logistic

Secondary/registry result

Percentage of Participants With an HbA1c Target Value of ≤6.5% (48 mmol/Mol)

Time frame:Week 40

HbA1c <6.5% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (number), percentage of participants	95% CI
Placebo	18.56	—
3 mg Orforglipron	66.39	—
12 mg Orforglipron	68.75	—
36 mg Orforglipron	68.91	—

Risk Difference (RD)48.0195% CI38.47 – 57.55p<.001Regression, Logistic

Risk Difference (RD)48.7995% CI39.11 – 58.47p<.001Regression, Logistic

Risk Difference (RD)52.4895% CI42.88 – 62.09p<.001Regression, Logistic

Secondary/registry result

Change From Baseline in Fasting Serum Glucose (FSG)

Time frame:Baseline, Week 40

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (least_squares_mean), milligram per deciliter (mg/dL)	95% CI
Placebo	-1.1	—
3 mg Orforglipron	-30.6	—
12 mg Orforglipron	-37.4	—
36 mg Orforglipron	-37.8	—

LS Mean Difference (Net)-29.495% CI-40.1 – -18.7p<.001Mixed Models Analysis

LS Mean Difference (Net)-36.395% CI-46.4 – -26.3p<.001Mixed Models Analysis

LS Mean Difference (Net)-36.795% CI-46.6 – -26.8p<.001Mixed Models Analysis

Secondary/registry result

Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG)

Time frame:Baseline, Week 40

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), milligram per deciliter (mg/dL)	95% CI
Placebo	-17.6	—
3 mg Orforglipron	-43.6	—
12 mg Orforglipron	-56.0	—
36 mg Orforglipron	-58.1	—

LS Mean Difference (Net)-26.095% CI-36.8 – -15.1p<.001Mixed Models Analysis

LS Mean Difference (Net)-38.495% CI-47.7 – -29.2p<.001Mixed Models Analysis

LS Mean Difference (Net)-40.595% CI-49.3 – -31.7p<.001Mixed Models Analysis

Secondary/protocol endpoint

Percentage of Participants With an HbA1c Target Value of < 7.0% (53 mmol/Mol)

Time frame:Week 40

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Percentage of Participants With an HbA1c Target Value of ≤6.5% (48 mmol/Mol)

Time frame:Week 40

HbA1c <6.5% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change From Baseline in Fasting Serum Glucose (FSG)

Time frame:Baseline, Week 40

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG)

Time frame:Baseline, Week 40

change from baseline, improvement

Cardiometabolic biomarkers

6 endpoints

Secondary/registry result

Percent Change From Baseline in Non-High-Density Lipoprotein (Non-HDL) Cholesterol

Time frame:Baseline, Week 40

Non-HDL cholesterol, change

percent change from baseline, improvement

Posted result

Group	Value (geometric_least_squares_mean), percent change	95% CI
Placebo	3.19	—
3 mg Orforglipron	-1.82	—
12 mg Orforglipron	-4.80	—
36 mg Orforglipron	-7.91	—

Geometric LS Mean Difference (Net)-4.8595% CI-10.33 – 0.96p0.100Mixed Models Analysis

Geometric LS Mean Difference (Net)-7.7595% CI-13.26 – -1.88p0.010Mixed Models Analysis

Geometric LS Mean Difference (Net)-10.7695% CI-15.53 – -5.71p<.001Mixed Models Analysis

Secondary/registry result

Percent Change From Baseline in Triglycerides

Time frame:Baseline, Week 40

Triglycerides, change

percent change from baseline, improvement

LOINC 2571-8

Posted result

Group	Value (geometric_least_squares_mean), percent change	95% CI
Placebo	0.0	—
3 mg Orforglipron	-9.1	—
12 mg Orforglipron	-16.5	—
36 mg Orforglipron	-14.0	—

Geometric LS Mean Difference (Net)-9.295% CI-18.3 – 0.9p0.072Mixed Models Analysis

Geometric LS Mean Difference (Net)-16.595% CI-24.5 – -7.7p<.001Mixed Models Analysis

Geometric LS Mean Difference (Net)-14.095% CI-22.0 – -5.3p0.002Mixed Models Analysis

Secondary/registry result

Change From Baseline in Systolic Blood Pressure (SBP)

Time frame:Baseline, Week 40

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Posted result

Group	Value (least_squares_mean), millimeters of mercury (mmHg)	95% CI
Placebo	-0.5	—
3 mg Orforglipron	-3.2	—
12 mg Orforglipron	-6.1	—
36 mg Orforglipron	-6.0	—

LS Mean Difference (Net)-2.795% CI-5.2 – -0.2p0.031Mixed Models Analysis

LS Mean Difference (Net)-5.695% CI-8.2 – -3.0p<.001Mixed Models Analysis

LS Mean Difference (Net)-5.595% CI-8.0 – -3.0p<.001Mixed Models Analysis

Secondary/protocol endpoint

Percent Change From Baseline in Non-High-Density Lipoprotein (Non-HDL) Cholesterol

Time frame:Baseline, Week 40

Non-HDL cholesterol, change

percent change from baseline, improvement

Secondary/protocol endpoint

Percent 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 (SBP)

Time frame:Baseline, Week 40

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Patient-reported / QoL

2 endpoints

Secondary/registry result

Change From Baseline in Short Form-36 Health Survey Version 2 (SF-36v2) Acute Form (Physical-Component and Mental-Component) Scores

Time frame:Baseline, Week 40

SF-36 physical

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), T-score	95% CI
PlaceboPhysical Component Score	2.25	—
Mental Component Score	0.09	—
3 mg OrforglipronPhysical Component Score	2.06	—
Mental Component Score	0.11	—
12 mg OrforglipronPhysical Component Score	2.21	—
Mental Component Score	-0.37	—
36 mg OrforglipronPhysical Component Score	1.58	—
Mental Component Score	-0.46	—

LS Mean Difference (Net)-0.1995% CI-1.63 – 1.26p0.801ANCOVA

LS Mean Difference (Net)-0.0495% CI-1.61 – 1.54p0.964ANCOVA

LS Mean Difference (Net)-0.6695% CI-2.25 – 0.92p0.410ANCOVA

LS Mean Difference (Net)0.0195% CI-1.89 – 1.91p0.990ANCOVA

LS Mean Difference (Net)-0.4695% CI-2.17 – 1.24p0.592ANCOVA

LS Mean Difference (Net)-0.5695% CI-2.49 – 1.37p0.571ANCOVA

Secondary/protocol endpoint

Change From Baseline in Short Form-36 Health Survey Version 2 (SF-36v2) Acute Form (Physical-Component and Mental-Component) 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

Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes.
The New England journal of medicine2025 Sep 18PMID40544435doi:10.1056/NEJMoa2505669via clinicaltrials gov reference derived + pubmed nct search

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableClinicalTrials.gov results section

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.