Orforglipron demonstrates compelling efficacy with injectable GLP-1 medicines in complete Phase 3 results
Posted on June 23, 2025
Eli Lilly releases ACHIEVE-1, a Phase 3 trial evaluating the safety and efficacy of orforglipron compared to placebo in adults with type 2 diabetes and inadequate glycemic control with diet and exercise alone. Orforglipron is an oral small molecule glucagon-like peptide-1 receptor agonist, taken without food and water restrictions, to complete a Phase 3 trial. After 40 weeks, all three doses of orforglipron achieved the primary endpoint of superior A1C reduction. The 12 mg and 36 mg doses showed clinically meaningful and statistically significant reductions in body weight vs. placebo. Orforglipron had a safety profile similar to the established GLP-1 class, and the most frequently reported adverse events were gastrointestinal-related.
“The ACHIEVE-1 trial demonstrated that orforglipron, a novel oral small-molecule GLP-1, achieved clinically meaningful reductions in A1C and body weight over 40 weeks in adults with type 2 diabetes,” said Dr. Julio Rosenstock, senior scientific advisor for Velocity Clinical Research at Medical City Dallas, clinical professor of medicine, University of Texas Southwestern Medical Center, and lead trial investigator. “The early onset of glycemic improvement, observed as soon as four weeks, reinforces the therapeutic potential of orforglipron as an effective, oral GLP-1 therapy for early type 2 diabetes treatment. These findings support further investigation in broader populations and longer-duration studies.”
| Full Results | |||||
| Orforglipron
3 mg |
Orforglipron
12 mg |
Orforglipron
36 mg |
Placebo
|
||
| Primary Endpoint | |||||
| A1C reduction from
baseline of 8.0 %i |
Efficacy estimand | 1.3 % | 1.6 % | 1.5 % | 0.1 % |
| Treatment-regimen
estimand4 |
1.2 % | 1.5 % | 1.5 % | 0.4 % | |
| Key Secondary Endpointsii | |||||
| Percent weight reduction
from baseline of 90.2 kg (198.9 lbs)i,iii |
Efficacy estimand | 4.7 % | 6.1 % | 7.9 % | 1.6 % |
| Treatment-regimen
estimand |
4.5 % | 5.8 % | 7.6 % | 1.7 % | |
| Weight reduction from
baseline of 90.2 kg (198.9 lbs)i,iii |
Efficacy estimand | 4.4 kg (9.7 lbs) |
5.5 kg (12.2 lbs) |
7.3 kg (16.0 lbs) |
1.3 kg
(2.9 lbs) |
| Treatment-regimen estimand |
4.2 kg
(9.3 lbs) |
5.2 kg
(11.5 lbs) |
7.2 kg
(15.8 lbs) |
1.5 kg
(3.4 lbs) |
|
| Percent of participants
achieving A1C <7 %i |
Efficacy estimand | 72.9 % | 76.2 % | 74.9 % | 28.0 % |
| Treatment-regimen
estimand |
68.1 % | 72.9 % | 72.7 % | 33.0 % | |
| Percent of participants
achieving A1C ≤6.5 %i,ii |
Efficacy estimand | 61.5 % | 62.3 % | 66.0 % | 13.5 % |
| Treatment-regimen estimand |
56.9 % | 58.1 % | 61.9 % | 14.9 % | |
| Percent of participants achieving A1C <5.7 %iii |
Efficacy estimand | 17.7 % | 25.8 % | 23.9 % | 3.8 % |
| Treatment-regimen
estimand |
16.8 % | 23.9 % | 21.5 % | 3.8 % | |
| Fasting serum glucose reduction from baselineof 147.5 mg/dLi |
Efficacy estimand | 30.6 mg/dL | 37.4 mg/dL | 37.8 mg/dL | 1.1 mg/dL |
| Treatment-regimen
estimand |
30.7 mg/dL | 36.5 mg/dL | 34.7 mg/dL | 10.8 mg/dL | |
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