Primary outcome
What ACHIEVE-5 measured first
| Placebon=141 | 3 mg Orforglipron QDn=137 | 12 mg Orforglipron QDn=132 | 36 mg Orforglipron QDn=136 |
|---|---|---|---|
| -0.77(0.078) | -1.54(0.097) | -2.05(0.098) | -1.90(0.111) |
Phase 3 · Orforglipron
ACHIEVE-5 trial results
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
Change From Baseline in Hemoglobin A1c (HbA1c) (percentage of HbA1c), Baseline, Week 40. Placebo: -0.77; 3 mg Orforglipron QD: -1.54; 12 mg Orforglipron QD: -2.05; 36 mg Orforglipron QD: -1.90.
- Participants
- 546
- Status
- completed
- Completed
- 2025-09-15
- Sponsor
- Eli Lilly and Company
As posted on ClinicalTrials.gov (NCT06109311), updated at source Oct 1, 2026. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.
Side effects by arm
Side effects in ACHIEVE-5
Percent of participants affected, Baseline to end of safety follow-up (up to 42 weeks). The most common events the registry lists.
| Event | Placebo | 3 mg Orforglipron QD | 12 mg Orforglipron QD | 36 mg Orforglipron QD |
|---|---|---|---|---|
| Any serious event | 4.3% | 5.1% | 6.8% | 7.4% |
| Nausea | 4.3% | 21.2% | 28% | 30.4% |
| Diabetic retinopathy | 27.9% | 17.5% | 15.9% | 23.7% |
| Vomiting | 0% | 8% | 15.2% | 21.5% |
| Decreased appetite | 4.3% | 13.9% | 15.9% | 20.7% |
| Diarrhoea | 7.1% | 19% | 13.6% | 16.3% |
| Constipation | 4.3% | 14.6% | 11.4% | 7.4% |
| Lipase increased | 2.9% | 4.4% | 9.1% | 9.6% |
| Dyspepsia | 2.9% | 5.8% | 9.1% | 5.9% |
| Blood creatine phosphokinase increased | 1.4% | 4.4% | 4.5% | 8.9% |
| Influenza | 8.6% | 1.5% | 1.5% | 5.2% |
| Nasopharyngitis | 7.9% | 7.3% | 3% | 5.9% |
| Abdominal distension | 1.4% | 2.9% | 7.6% | 7.4% |
| Back pain | 2.9% | 3.6% | 4.5% | 6.7% |
| Cataract | 6.4% | 3.6% | 3% | 1.5% |
| Eructation | 0% | 3.6% | 6.1% | 1.5% |
| Abdominal pain upper | 2.9% | 2.2% | 1.5% | 5.9% |
| Upper respiratory tract infection | 5.7% | 5.8% | 4.5% | 5.9% |
| Headache | 1.4% | 2.9% | 5.3% | 5.9% |
| Glomerular filtration rate decreased | 2.9% | 5.8% | 3.8% | 3% |
| Dizziness | 4.3% | 5.8% | 2.3% | 2.2% |
| Macular oedema | 2.1% | 5.1% | 3% | 5.2% |
| Gastrooesophageal reflux disease | 0% | 2.2% | 3% | 5.2% |
| Amylase increased | 0% | 2.2% | 3.8% | 5.2% |
| Hyperglycaemia | 2.9% | 2.2% | 0.8% | 5.2% |
| Asthenia | 2.1% | 2.9% | 4.5% | 4.4% |
Secondary outcomes
What else it measured
| Placebon=141 | 3 mg Orforglipron QDn=137 | 12 mg Orforglipron QDn=132 | 36 mg Orforglipron QDn=136 |
|---|---|---|---|
| 23.69 | 60.74 | 80.76 | 69.16 |
| Placebon=141 | 3 mg Orforglipron QDn=137 | 12 mg Orforglipron QDn=132 | 36 mg Orforglipron QDn=136 |
|---|---|---|---|
| 11.09 | 45.94 | 69.12 | 60.07 |
| Placebon=141 | 3 mg Orforglipron QDn=137 | 12 mg Orforglipron QDn=132 | 36 mg Orforglipron QDn=136 |
|---|---|---|---|
| -35.3(2.36) | -40.5(2.84) | -48.0(2.74) | -44.5(2.69) |
| Placebon=141 | 3 mg Orforglipron QDn=137 | 12 mg Orforglipron QDn=132 | 36 mg Orforglipron QDn=136 |
|---|---|---|---|
| 0.6(0.44) | -2.7(0.52) | -5.8(0.58) | -6.1(0.68) |
| Placebon=141 | 3 mg Orforglipron QDn=137 | 12 mg Orforglipron QDn=132 | 36 mg Orforglipron QDn=136 |
|---|---|---|---|
| 0.5(0.39) | -2.2(0.48) | -5.0(0.49) | -5.2(0.64) |
| Placebon=141 | 3 mg Orforglipron QDn=137 | 12 mg Orforglipron QDn=132 | 36 mg Orforglipron QDn=136 |
|---|---|---|---|
| -1.13(2.679) | -3.90(2.346) | -7.64(2.597) | -7.81(2.450) |
| Placebon=141 | 3 mg Orforglipron QDn=137 | 12 mg Orforglipron QDn=132 | 36 mg Orforglipron QDn=136 |
|---|---|---|---|
| -4.73(3.398) | -4.80(3.149) | -17.45(3.040) | -14.71(3.144) |
| Placebon=141 | 3 mg Orforglipron QDn=137 | 12 mg Orforglipron QDn=132 | 36 mg Orforglipron QDn=136 |
|---|---|---|---|
| 0.0(1.03) | -1.9(0.94) | -3.2(1.13) | -2.2(1.26) |
| Placebon=141 | 3 mg Orforglipron QDn=137 | 12 mg Orforglipron QDn=132 | 36 mg Orforglipron QDn=136 |
|---|---|---|---|
| 21.4(2.41) | 8.9(1.57) | 10.2(1.89) | 8.4(2.28) |
| Placebon=141 | 3 mg Orforglipron QDn=137 | 12 mg Orforglipron QDn=132 | 36 mg Orforglipron QDn=136 |
|---|---|---|---|
| 16.10 | 35.42 | 52.61 | 50.56 |
| Placebon=141 | 3 mg Orforglipron QDn=137 | 12 mg Orforglipron QDn=132 | 36 mg Orforglipron QDn=136 |
|---|---|---|---|
| 4.24 | 15.70 | 23.34 | 27.38 |
| Placebon=141 | 3 mg Orforglipron QDn=137 | 12 mg Orforglipron QDn=132 | 36 mg Orforglipron QDn=136 |
|---|---|---|---|
| 2.52 | 6.18 | 9.90 | 14.12 |
The trial
How ACHIEVE-5 was run
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.
- 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.
- 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.
- 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.
- 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.
Who could join the trial
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.
Published papers
Papers from ACHIEVE-5
Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.
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