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Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

Short name ACHIEVE-5

NCTNCT06109311 (opens ClinicalTrials.gov in a new tab)Other id18567Other idJ2A-MC-GZGWOther idU1111-1294-2797Other id2023-507280-18-00
Open at ClinicalTrials.govAsk about this trial

Overview

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

United States, Brazil, China, Japan, Puerto Rico, Romania

Start
10 Nov 2023
Primary completion
15 Sept 2025
Completion
15 Sept 2025
First posted
31 Oct 2023
Last update posted
1 Oct 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-5

    NCT06109311

    10 Nov 2023 to 15 Sept 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 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.

Interventions

  • OrforglipronDrug
  • PlaceboDrug

Arms4

  • Placebo comparator

    Placebo

    Participants 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.

  • Experimental

    3 mg Orforglipron QD

    Participants 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.

  • Experimental

    12 mg Orforglipron QD

    Participants 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.

  • Experimental

    36 mg Orforglipron QD

    Participants 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.

Primary outcomes1

Outcomes the sponsor listed as primary.

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

Secondary outcomes(13)

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

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

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

  5. Change From Baseline in Body Weight (kg)

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

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

    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 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.

  7. Percent Change From Baseline in Triglycerides

    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 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.

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

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

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

    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 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.

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

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

    Time frame · Week 40

    Registry description

    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 \[Yes or No\].

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

    Time frame · Week 40

    Registry description

    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 \[Yes or No\].

  13. 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 Hemoglobin A1c (HbA1c)

GroupValue (percentage of HbA1c)Spread
Placebo-0.770.078
3 mg Orforglipron QD-1.540.097
12 mg Orforglipron QD-2.050.098
36 mg Orforglipron QD-1.900.111
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)
Placebo23.69
3 mg Orforglipron QD60.74
12 mg Orforglipron QD80.76
36 mg Orforglipron QD69.16
Secondary outcomeNumber· Week 40

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

GroupValue (percentage of participants)
Placebo11.09
3 mg Orforglipron QD45.94
12 mg Orforglipron QD69.12
36 mg Orforglipron QD60.07
Secondary outcomeLeast squares mean· Baseline, Week 40

Change From Baseline in Fasting Serum Glucose (FSG)

GroupValue (milligrams per deciliter (mg/dL))Spread
Placebo-35.32.36
3 mg Orforglipron QD-40.52.84
12 mg Orforglipron QD-48.02.74
36 mg Orforglipron QD-44.52.69
Secondary outcomeLeast squares mean· Baseline, Week 40

Percent Change From Baseline in Body Weight

GroupValue (Percent change)Spread
Placebo0.60.44
3 mg Orforglipron QD-2.70.52
12 mg Orforglipron QD-5.80.58
36 mg Orforglipron QD-6.10.68
Secondary outcomeLeast squares mean· Baseline, Week 40

Change From Baseline in Body Weight (kg)

GroupValue (Kilogram (kg))Spread
Placebo0.50.39
3 mg Orforglipron QD-2.20.48
12 mg Orforglipron QD-5.00.49
36 mg Orforglipron QD-5.20.64
Secondary outcomeLeast squares mean· Baseline, Week 40

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

GroupValue (Percent change)Spread
Placebo-1.132.679
3 mg Orforglipron QD-3.902.346
12 mg Orforglipron QD-7.642.597
36 mg Orforglipron QD-7.812.450
Secondary outcomeLeast squares mean· Baseline, Week 40

Percent Change From Baseline in Triglycerides

GroupValue (Percent change)Spread
Placebo-4.733.398
3 mg Orforglipron QD-4.803.149
12 mg Orforglipron QD-17.453.040
36 mg Orforglipron QD-14.713.144

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
PlaceboParticipants received matching placebo administered orally QD and insulin glargine therapy 100 U/mL administered SC QD, over a period of 40 weeks.0 / 1406 / 140111 / 140
3 mg Orforglipron QDParticipants received oral orforglipron, initiated at 1 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.0 / 1377 / 137110 / 137
12 mg Orforglipron QDParticipants 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.0 / 1329 / 132105 / 132
36 mg Orforglipron QDParticipants 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.1 / 13510 / 135114 / 135

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 · 2026

11 results

Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial.

Giorgino et al. 2026JAMA

PMID 42251769DOI 10.1001/jama.2026.9512PUB-42251769

Full text at the publisher11 results
Publisher pageSee results (11)

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 (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.

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