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Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

Short name ACHIEVE-1

NCTNCT05971940 (opens ClinicalTrials.gov in a new tab)Other id18564Other idJ2A-MC-GZGTOther idU1111-1290-5157
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
559 participants (actual)
Sponsor
Eli Lilly and Company · Industry
Design
Randomized · Double masking
Countries
6 countries

United States, China, India, Japan, Mexico, Puerto Rico

Start
9 Aug 2023
Primary completion
3 Apr 2025
Completion
3 Apr 2025
First posted
2 Aug 2023
Last update posted
3 Sept 2026
Conditions
Type 2 Diabetes

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2023202420252026
  1. Ph 3

    ACHIEVE-1

    NCT05971940

    9 Aug 2023 to 3 Apr 2025

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The main purpose of this study is to determine safety and efficacy of orforglipron compared with placebo in adult participants with type 2 diabetes and inadequate glycemic control with diet and exercise alone. The study will last approximately 54 weeks.

Interventions

  • OrforglipronDrug
  • PlaceboDrug

Arms4

  • Placebo comparator

    Placebo

    Participants received once daily (QD) doses of orforglipron-matching placebo capsules administered orally, over a period of 40 weeks.

  • Experimental

    3 mg Orforglipron

    Participants received orforglipron capsules administered orally QD, starting at 1 milligram (mg) and increasing by 1 mg every 4 weeks until reaching a targeted dose of 3 mg, which was then maintained up to week 40.

  • Experimental

    12 mg Orforglipron

    Participants received orforglipron capsules administered orally QD, starting at 1 mg and increasing every 4 weeks until reaching a targeted dose of 12 mg, which was then maintained up to week 40.

  • Experimental

    36 mg Orforglipron

    Participants received orforglipron capsules administered orally QD, starting at 1 mg and increasing every 4 weeks until reaching a targeted dose of 36 mg, which was then maintained up to week 40.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Change From Baseline in HbA1c

    Time frame · Baseline, Week 40

    Registry description

    * 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 prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured.

Secondary outcomes(11)

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

    Time frame · Week 40

    Registry description

    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 prior use of any antihyperglycemic medication (yes or no).

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

    Time frame · Week 40

    Registry description

    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 prior use of any antihyperglycemic medication (yes or no).

  3. Change From Baseline in Fasting Serum Glucose (FSG)

    Time frame · Baseline, Week 40

    Registry description

    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 prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured.

  4. Percent Change From Baseline in Body Weight

    Time frame · Baseline, Week 40

    Registry description

    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 prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured.

  5. Change From Baseline in Body Weight

    Time frame · Baseline, Week 40

    Registry description

    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 prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured.

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

    Time frame · Baseline, Week 40

    Registry description

    Values represented under "Geometric LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a MMRM with analysis : log (Actual Measurement/Baseline) = country, treatment by time, log(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 prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured.

  7. Percent Change From Baseline in Triglycerides

    Time frame · Baseline, Week 40

    Registry description

    Values represented under "Geometric LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a MMRM with analysis : log (Actual Measurement/Baseline) = country, treatment by time, log(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 prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured.

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

    Time frame · Baseline, Week 40

    Registry description

    The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Post meal, Midday Premeal, Midday 2-hour Post meal, Evening Premeal, Evening 2-hour Post meal and Bedtime. The daily average was calculated as the average of the 7 blood glucose values collected on a particular day. 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 prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured.

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

    Time frame · Week 40

    Registry description

    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 prior use of any antihyperglycemic medication (yes or no).

  10. Change From Baseline in Systolic Blood Pressure (SBP)

    Time frame · Baseline, Week 40

    Registry description

    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 prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured.

  11. 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

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeLeast squares mean· Baseline, Week 40

Change From Baseline in HbA1c

GroupValue (percentage of HbA1c)Spread
Placebo-0.150.113
3 mg Orforglipron-1.260.114
12 mg Orforglipron-1.590.087
36 mg Orforglipron-1.450.104
Secondary and other outcome results(7)
Secondary outcomeNumber· Week 40

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

GroupValue (percentage of participants)
Placebo37.11
3 mg Orforglipron78.15
12 mg Orforglipron81.25
36 mg Orforglipron78.99
Secondary outcomeNumber· Week 40

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

GroupValue (percentage of participants)
Placebo18.56
3 mg Orforglipron66.39
12 mg Orforglipron68.75
36 mg Orforglipron68.91
Secondary outcomeLeast squares mean· Baseline, Week 40

Change From Baseline in Fasting Serum Glucose (FSG)

GroupValue (milligram per deciliter (mg/dL))Spread
Placebo-1.14.01
3 mg Orforglipron-30.63.66
12 mg Orforglipron-37.43.08
36 mg Orforglipron-37.82.94
Secondary outcomeLeast squares mean· Baseline, Week 40

Percent Change From Baseline in Body Weight

GroupValue (percent change)Spread
Placebo-1.60.43
3 mg Orforglipron-4.70.47
12 mg Orforglipron-6.10.55
36 mg Orforglipron-7.90.58
Secondary outcomeLeast squares mean· Baseline, Week 40

Change From Baseline in Body Weight

GroupValue (kilogram (kg))Spread
Placebo-1.30.36
3 mg Orforglipron-4.40.43
12 mg Orforglipron-5.50.49
36 mg Orforglipron-7.30.55
Secondary outcomeGeometric least squares mean· Baseline, Week 40

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

GroupValue (percent change)Spread
Placebo3.192.085
3 mg Orforglipron-1.822.193
12 mg Orforglipron-4.802.273
36 mg Orforglipron-7.911.760
Secondary outcomeGeometric least squares mean· Baseline, Week 40

Percent Change From Baseline in Triglycerides

GroupValue (percent change)Spread
Placebo0.03.56
3 mg Orforglipron-9.13.61
12 mg Orforglipron-16.53.06
36 mg Orforglipron-14.02.84

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
PlaceboParticipants received QD doses of orforglipron-matching placebo capsules administered orally, over a period of 40 weeks.1 / 1385 / 138110 / 138
3 mg OrforglipronParticipants received orforglipron capsules administered orally QD, starting at 1 mg and increasing by 1 mg every 4 weeks until reaching a targeted dose of 3 mg, which was then maintained up to week 40.2 / 1438 / 143118 / 143
12 mg OrforglipronParticipants received orforglipron capsules administered orally QD, starting at 1 mg and increasing every 4 weeks until reaching a targeted dose of 12 mg, which was then maintained up to week 40.1 / 1377 / 137118 / 137
36 mg OrforglipronParticipants received orforglipron capsules administered orally QD, starting at 1 mg and increasing every 4 weeks until reaching a targeted dose of 36 mg, which was then maintained up to week 40.0 / 1414 / 141123 / 141

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2025

10 results

Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes.

Rosenstock et al. 2025The New England journal of medicinecited by 71

PMID 40544435DOI 10.1056/nejmoa2505669PUB-40544435

Full text at the publisher10 results
Publisher pageSee results (10)

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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

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