Eli Lilly announced positive topline results from the ATTAIN-2 Phase 3 trial of orforglipron, an oral GLP-1 receptor agonist for obesity and type 2 diabetes.
The trial confirmed significant weight loss, improved A1C levels, and cardiometabolic benefits across all tested doses at 72 weeks. With these results, Lilly now has the full data package needed for global regulatory submissions.
Headline Results
- Primary endpoint met: Superior body weight reduction versus placebo.
- Highest dose (36 mg): Average 10.5% weight loss (22.9 lbs) vs. 2.2% (5.1 lbs) with placebo.
- A1C reductions: 1.3% to 1.8% across doses, from a baseline of 8.1%.
- Diabetes remission marker: 75% of patients on 36 mg achieved A1C ≤6.5%.
- Inflammation marker: hsCRP reduced by 50.6% at the highest dose.
Expert Reactions
Dr. Louis J. Aronne, obesity specialist, highlighted:
“Orforglipron could expand options for patients preferring oral therapies without compromising efficacy, safety, or tolerability.”
Lilly executive VP Kenneth Custer emphasized speed:
“With these data, we are moving urgently toward global submissions. If approved, orforglipron can scale worldwide as a once-daily pill.”
Detailed Efficacy (Efficacy Estimand)
|
Endpoint |
Orforglipron |
12mg |
36mg |
Placebo |
|
Weigh Change |
-5.5% (-12.1 lbs) |
-7.8% (-17.4 lbs) |
-10.5% (-22.9 lbs) |
-2.2% (-5.1 lbs) |
|
≥10% weight loss |
23.9% |
35.5% |
50.1% |
7.0% |
|
≥15% weight loss |
7.3% |
17.7% |
28.4% |
1.9% |
|
A1C reduction |
-1.3% |
-1.6% |
-1.8% |
-0.1% |
|
A1C <7% |
70.0% |
78% |
85.1% |
23% |
|
A1C ≤6.5% |
56.2% |
67.5% |
75.0% |
10.6% |
Treatment-Regimen Estimand
Results held consistent under a second analysis that accounted for adherence and treatment interruptions. Weight reduction ranged from -]5.1% (6 mg) to -9.6% (36 mg), versus -2.5% with placebo.
Safety Profile
Orforglipron’s safety was in line with injectable GLP-1s.
- Most common side effects: nausea, vomiting, diarrhea, constipation, dyspepsia.
- GI events were mild-to-moderate in severity.
- Discontinuation rates due to adverse events: 6.1% (6 mg), 10.6% (12 mg and 36 mg), vs. 4.6% placebo.
- No hepatic safety signals observed.
About the ATTAIN-2 Trial
- Design: Phase 3, 72-week, randomized, double-blind, placebo-controlled.
- Participants: Over 1,600 adults with obesity or overweight and type 2 diabetes.
- Sites: U.S., Argentina, Australia, Brazil, China, Czechia, Germany, Greece, India, South Korea, Puerto Rico.
- Dosing: Patients started at 1 mg daily, increasing stepwise to final doses (6, 12, or 36 mg).
- Objective: Test superiority of orforglipron over placebo in weight reduction at 72 weeks.
This study is part of Lilly’s ATTAIN Phase 3 program, which has enrolled over 4,500 participants globally.
About Orforglipron
- A once-daily oral small molecule GLP-1 receptor agonist.
- No food or water restrictions required.
- Discovered by Chugai Pharmaceutical and licensed by Lilly in 2018.
- Being studied for obesity, type 2 diabetes, obstructive sleep apnea, and hypertension in adults with obesity.
What’s Next
- Lilly will present detailed ATTAIN-2 results at a future medical meeting and in a peer-reviewed journal.
- Global regulatory submissions are imminent.
If approved, orforglipron would be the first oral GLP-1 therapy with efficacy comparable to injectables, potentially redefining obesity and diabetes treatment worldwide.
