Eli Lilly and Company has announced successful results from the Phase 3 ACHIEVE-1 trial for orforglipron, a once-daily oral GLP-1 receptor agonist being developed for type 2 diabetes. The investigational drug demonstrated strong efficacy in lowering blood glucose and promoting weight loss, with a safety profile consistent with existing injectable GLP-1 treatments.
A New Option for Managing Type 2 Diabetes
Orforglipron is the first oral small molecule in its class to complete a Phase 3 trial. Unlike peptide-based GLP-1 drugs, this pill does not require refrigeration or administration with food or water restrictions, potentially simplifying diabetes treatment for millions worldwide.
In the ACHIEVE-1 study, orforglipron met its primary endpoint, reducing A1C levels by 1.3% to 1.6% across all tested doses from a baseline of 8.0%. At the highest dose, over 65% of patients reached an A1C below 6.5%, the benchmark for diabetes control set by the American Diabetes Association.
Significant Weight Loss Observed
Weight management, a critical component of diabetes care, also showed encouraging results. Participants lost an average of 16 lbs (7.9%) at the highest dose over 40 weeks, and weight loss had not yet plateaued, suggesting further reductions might occur with extended treatment.
Safety Consistent with Existing Therapies
The most commonly reported side effects were gastrointestinal, including nausea, diarrhea, and constipation—similar to injectable GLP-1 drugs. Adverse events were generally mild to moderate, and discontinuation rates remained low.
Global Launch Plans and Future Trials
Lilly plans to submit orforglipron for weight management approval by the end of 2025, followed by diabetes-related filings in 2026. The ACHIEVE program spans seven trials and over 6,000 participants, with additional data expected later this year.
This advancement supports Lilly’s broader goal to combat chronic conditions like obesity and diabetes, which are projected to affect 760 million people globally by 2050.
Cosmael ThinkLab Commentary
Orforglipron represents a major leap in diabetes care. As a non-peptide, room-temperature-stable oral therapy, it may remove significant barriers to treatment access and adherence. Its promising efficacy, combined with a tolerable safety profile, could make it a game-changer—particularly in regions where injectable therapies face logistical and patient compliance challenges.
If approved, it would be a landmark moment in the evolution of GLP-1 treatments.
Source: Eli Lilly and Company, Press Release, April 17, 2025
For further reading: Lilly.com/news