Phase 3 · Orforglipron

ACHIEVE-1 trial results

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

Change From Baseline in HbA1c (percentage of HbA1c), Baseline, Week 40. Placebo: -0.15; 3 mg Orforglipron: -1.26; 12 mg Orforglipron: -1.59; 36 mg Orforglipron: -1.45.

Participants
559
Status
completed
Completed
2025-04-03
Sponsor
Eli Lilly and Company

As posted on ClinicalTrials.gov (NCT05971940), updated at source Sep 3, 2026. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What ACHIEVE-1 measured first

Change From Baseline in HbA1cpercentage of HbA1c · Baseline, Week 40 · least squares mean
Placebon=1383 mg Orforglipronn=14312 mg Orforglipronn=13736 mg Orforglipronn=141
-0.15(0.113)-1.26(0.114)-1.59(0.087)-1.45(0.104)
Side effects by arm

Side effects in ACHIEVE-1

Percent of participants affected, Baseline to end of safety follow-up (up to 42 weeks). The most common events the registry lists.

EventPlacebo3 mg Orforglipron12 mg Orforglipron36 mg Orforglipron
Any serious event3.6%5.6%5.1%2.8%
Hyperglycaemia26.8%7.7%4.4%6.4%
Diarrhoea9.4%18.9%21.2%25.5%
Dyspepsia7.2%11.9%21.2%15.6%
Nausea2.2%12.6%19%17%
Diabetic retinopathy15.2%14.7%5.8%17%
Constipation3.6%8.4%16.8%14.2%
Vomiting1.4%4.9%6.6%14.2%
Decreased appetite2.2%3.5%10.2%12.1%
Abdominal distension8%4.2%5.1%11.3%
Headache5.8%7%5.8%7.8%
Nasopharyngitis5.8%3.5%7.3%2.8%
Eructation0%3.5%4.4%7.1%
Abdominal pain upper1.4%0%5.8%2.8%
Hypertension5.8%4.2%2.9%3.5%
Gastrooesophageal reflux disease1.4%2.1%5.1%5%
Lipase increased2.2%2.8%5.1%2.1%
Abdominal pain1.4%0.7%2.9%5%
Dyslipidaemia4.3%3.5%0.7%5%
Pyrexia3.6%3.5%4.4%2.1%
Blood creatine phosphokinase increased4.3%2.1%1.5%0.7%
Dizziness1.4%4.2%2.9%3.5%
Fatigue3.6%2.1%0.7%2.8%
Influenza2.2%1.4%3.6%1.4%
Glomerular filtration rate decreased3.6%2.1%0.7%0%
Hyperlipidaemia3.6%0.7%2.2%2.1%
Secondary outcomes

What else it measured

Percentage of Participants With an HbA1c Target Value of < 7.0% (53 mmol/Mol)percentage of participants · Week 40 · number
Placebon=973 mg Orforglipronn=11912 mg Orforglipronn=11236 mg Orforglipronn=119
37.1178.1581.2578.99
Percentage of Participants With an HbA1c Target Value of ≤6.5% (48 mmol/Mol)percentage of participants · Week 40 · number
Placebon=973 mg Orforglipronn=11912 mg Orforglipronn=11236 mg Orforglipronn=119
18.5666.3968.7568.91
Change From Baseline in Fasting Serum Glucose (FSG)milligram per deciliter (mg/dL) · Baseline, Week 40 · least squares mean
Placebon=1333 mg Orforglipronn=13612 mg Orforglipronn=13036 mg Orforglipronn=136
-1.1(4.01)-30.6(3.66)-37.4(3.08)-37.8(2.94)
Percent Change From Baseline in Body Weightpercent change · Baseline, Week 40 · least squares mean
Placebon=1383 mg Orforglipronn=14312 mg Orforglipronn=13736 mg Orforglipronn=141
-1.6(0.43)-4.7(0.47)-6.1(0.55)-7.9(0.58)
Change From Baseline in Body Weightkilogram (kg) · Baseline, Week 40 · least squares mean
Placebon=1383 mg Orforglipronn=14312 mg Orforglipronn=13736 mg Orforglipronn=141
-1.3(0.36)-4.4(0.43)-5.5(0.49)-7.3(0.55)
Percent Change From Baseline in Non-High-Density Lipoprotein (Non-HDL) Cholesterolpercent change · Baseline, Week 40 · geometric least squares mean
Placebon=1353 mg Orforglipronn=13612 mg Orforglipronn=13136 mg Orforglipronn=137
3.19(2.085)-1.82(2.193)-4.80(2.273)-7.91(1.760)
Percent Change From Baseline in Triglyceridespercent change · Baseline, Week 40 · geometric least squares mean
Placebon=1353 mg Orforglipronn=13612 mg Orforglipronn=13036 mg Orforglipronn=136
0.0(3.56)-9.1(3.61)-16.5(3.06)-14.0(2.84)
Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG)milligram per deciliter (mg/dL) · Baseline, Week 40 · least squares mean
Placebon=1283 mg Orforglipronn=13812 mg Orforglipronn=12936 mg Orforglipronn=130
-17.6(3.99)-43.6(3.73)-56.0(2.29)-58.1(1.80)
Percentage of Participants With Greater Than or Equal to (≥) 5% Body Weight Reductionpercentage of participants · Week 40 · number
Placebon=963 mg Orforglipronn=11912 mg Orforglipronn=11136 mg Orforglipronn=119
14.5847.0658.5666.39
Change From Baseline in Systolic Blood Pressure (SBP)millimeters of mercury (mmHg) · Baseline, Week 40 · least squares mean
Placebon=1383 mg Orforglipronn=14312 mg Orforglipronn=13736 mg Orforglipronn=141
-0.5(0.88)-3.2(0.91)-6.1(0.97)-6.0(0.91)
Change From Baseline in Short Form-36 Health Survey Version 2 (SF-36v2) Acute Form (Physical-Component and Mental-Component) ScoresT-score · Baseline, Week 40 · least squares mean
MeasurePlacebon=1363 mg Orforglipronn=14312 mg Orforglipronn=13736 mg Orforglipronn=139
Physical Component Score2.25(0.592)2.06(0.513)2.21(0.574)1.58(0.632)
Mental Component Score0.09(0.689)0.11(0.687)-0.37(0.587)-0.46(0.777)
The trial

How ACHIEVE-1 was run

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.

  • Placebo: Participants received once daily (QD) doses of orforglipron-matching placebo capsules administered orally, over a period of 40 weeks.
  • 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.
  • 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.
  • 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.
Who could join the trial

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

Published papers

Papers from ACHIEVE-1

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

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