What ACHIEVE-3 measured first
| 12 mg Orforglipronn=326 | 36 mg Orforglipronn=322 | 7 mg Semaglutiden=325 | 14 mg Semaglutiden=351 |
|---|---|---|---|
| -1.91(0.058) | -2.16(0.051) | -1.11(0.063) | -1.45(0.061) |
A Phase 3, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Once Daily Oral LY3502970 Compared With Oral Semaglutide in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin (ACHIEVE-3)
Change From Baseline in Hemoglobin A1c (HbA1c) [Non-inferiority of 36 mg Orforglipron Versus 14 mg Semaglutide and 12 mg Orforglipron Versus 7 mg Semaglutide] (Percentage of HbA1c), Baseline, Week 52. 12 mg Orforglipron: -1.91; 36 mg Orforglipron: -2.16; 7 mg Semaglutide: -1.11; 14 mg Semaglutide: -1.45.
As posted on ClinicalTrials.gov (NCT06045221), updated at source Sep 15, 2026. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.
| 12 mg Orforglipronn=326 | 36 mg Orforglipronn=322 | 7 mg Semaglutiden=325 | 14 mg Semaglutiden=351 |
|---|---|---|---|
| -1.91(0.058) | -2.16(0.051) | -1.11(0.063) | -1.45(0.061) |
Percent of participants affected, Baseline to end of safety follow-up (up to 57 weeks). The most common events the registry lists.
| Event | 12 mg Orforglipron | 36 mg Orforglipron | 7 mg Semaglutide | 14 mg Semaglutide |
|---|---|---|---|---|
| Any serious event | 5% | 9.5% | 4.5% | 5.6% |
| Nausea | 26.4% | 27.4% | 13.1% | 21.2% |
| Diarrhoea | 21.7% | 23.4% | 13.1% | 18.1% |
| Vomiting | 17% | 16.5% | 7.7% | 10.4% |
| Hyperglycaemia | 5.9% | 4.7% | 16.2% | 8% |
| Diabetic retinopathy | 13.4% | 14.2% | 12.7% | 13.6% |
| Constipation | 13.2% | 13% | 7.7% | 8.9% |
| Dyspepsia | 11.3% | 10.4% | 4.2% | 7.8% |
| Eructation | 9.9% | 7.6% | 4% | 3.3% |
| Abdominal distension | 5.7% | 8% | 2.6% | 3.3% |
| Decreased appetite | 7.1% | 6.9% | 4.9% | 6.4% |
| Gastrooesophageal reflux disease | 5.7% | 6.1% | 2.8% | 4.2% |
| Hypertension | 2.8% | 3.5% | 4.7% | 6.1% |
| Abdominal pain | 5% | 5.4% | 3.1% | 3.3% |
| Flatulence | 5.2% | 2.8% | 3.5% | 1.6% |
| Headache | 5.2% | 3.8% | 4.5% | 4.5% |
| 12 mg Orforglipronn=326 | 36 mg Orforglipronn=322 | 7 mg Semaglutiden=325 | 14 mg Semaglutiden=351 |
|---|---|---|---|
| -1.91(0.058) | -2.16(0.051) | -1.11(0.063) | -1.45(0.061) |
| 12 mg Orforglipronn=424 | 36 mg Orforglipronn=423 | 7 mg Semaglutiden=426 | 14 mg Semaglutiden=425 |
|---|---|---|---|
| 80.04(1.97) | 85.41(1.80) | 54.63(2.45) | 66.12(2.27) |
| 12 mg Orforglipronn=424 | 36 mg Orforglipronn=423 | 7 mg Semaglutiden=426 | 14 mg Semaglutiden=425 |
|---|---|---|---|
| 71.76(2.26) | 76.82(2.14) | 40.87(2.38) | 50.88(2.42) |
| 12 mg Orforglipronn=424 | 36 mg Orforglipronn=423 | 7 mg Semaglutiden=426 | 14 mg Semaglutiden=425 |
|---|---|---|---|
| 25.44(2.24) | 37.09(2.56) | 7.84(1.27) | 12.54(1.64) |
| 12 mg Orforglipronn=331 | 36 mg Orforglipronn=323 | 7 mg Semaglutiden=325 | 14 mg Semaglutiden=356 |
|---|---|---|---|
| -6.7(0.34) | -9.2(0.40) | -3.7(0.27) | -5.3(0.30) |
| 12 mg Orforglipronn=331 | 36 mg Orforglipronn=323 | 7 mg Semaglutiden=325 | 14 mg Semaglutiden=356 |
|---|---|---|---|
| -6.6(0.34) | -8.9(0.39) | -3.6(0.26) | -5.0(0.29) |
| 12 mg Orforglipronn=326 | 36 mg Orforglipronn=321 | 7 mg Semaglutiden=326 | 14 mg Semaglutiden=353 |
|---|---|---|---|
| -55.2(1.77) | -60.1(1.55) | -28.9(2.49) | -40.2(2.33) |
| 12 mg Orforglipronn=262 | 36 mg Orforglipronn=244 | 7 mg Semaglutiden=254 | 14 mg Semaglutiden=278 |
|---|---|---|---|
| -69.4(1.60) | -74.9(1.40) | -51.2(2.10) | -61.4(1.48) |
| 12 mg Orforglipronn=424 | 36 mg Orforglipronn=423 | 7 mg Semaglutiden=426 | 14 mg Semaglutiden=425 |
|---|---|---|---|
| 59.18(2.55) | 69.49(2.39) | 36.89(2.53) | 49.39(2.57) |
| 12 mg Orforglipronn=424 | 36 mg Orforglipronn=423 | 7 mg Semaglutiden=426 | 14 mg Semaglutiden=425 |
|---|---|---|---|
| 28.23(2.34) | 43.46(2.54) | 13.18(1.84) | 20.95(2.08) |
| 12 mg Orforglipronn=424 | 36 mg Orforglipronn=423 | 7 mg Semaglutiden=426 | 14 mg Semaglutiden=425 |
|---|---|---|---|
| 11.99(1.65) | 23.21(2.17) | 4.99(1.19) | 6.45(1.25) |
| 12 mg Orforglipronn=331 | 36 mg Orforglipronn=323 | 7 mg Semaglutiden=325 | 14 mg Semaglutiden=356 |
|---|---|---|---|
| -4.5(0.55) | -5.4(0.65) | -2.0(0.58) | -2.7(0.59) |
The main purpose of this study is to assess efficacy and safety of orforglipron compared with oral semaglutide in participants with Type 2 diabetes and inadequate glycemic control with metformin.The study will last around 61 weeks.
Inclusion Criteria: * Have Type 2 Diabetes * Have HbA1c ≥7.0% (53 mmol/mol) to ≤10.5% (91 mmol/mol), as determined by the central laboratory at screening. * Have been on stable diabetes treatment with metformin ≥1500 milligram (mg)/day during the 90 days prior to screening and maintained through randomization. * Are of stable body 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 Exclusion Criteria: * Have Type 1 Diabetes * Are currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema, for example, laser photocoagulation or intravitreal injections of anti-vascular endothelial growth factor inhibitors. * Have a history of ketoacidosis or hyperosmolar state or coma within the last 6 months prior to screening, or between screening and randomization. * Have a New York Heart Association functional classification IV congestive heart failure. * Have an estimated glomerular filtration rate (eGFR) \<45 milliliter/minute (mL/min)/1.73 square meter (m²) or lower than the country-specific threshold for discontinuing metformin therapy per local label as determined by the central laboratory at screening. * Have a serum calcitonin level of ≥35 nanogram/Liter (ng/L), as determined by the central laboratory at screening. * Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years.
Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.