In April 2025, global pharmaceutical company Eli Lilly announced successful results from the Phase 3 clinical trial of orforglipron, an investigational oral glucagon-like peptide-1 (GLP-1) receptor agonist, signaling a potentially transformative shift in the obesity treatment market. Achieving Phase 3 success as the first oral GLP-1 obesity drug marks a significant milestone, especially considering the market's historical reliance on injectable formulations, and holds the promise of dramatically improving patient convenience.
Orforglipron Phase 3 Key Findings (FACT BASED)
The Phase 3 trial involved overweight or obese adults with type 2 diabetes and compared the orforglipron group to a placebo group over a 40-week period. The primary outcomes included:
- Weight Loss Efficacy: The orforglipron-treated group experienced an average weight reduction of 7.9% over the study duration. This result was statistically significant when compared to the weight changes in the placebo group. Specifically, the 12mg dosage group achieved an average weight loss of 5.2 kg, while the 36mg dosage group demonstrated an average weight loss of 7.3 kg.
- Glycemic Control: Orforglipron also demonstrated positive effects on blood sugar management. The treatment group showed an average reduction of 1.6% in HbA1c (glycated hemoglobin) levels, with over 65% of participants reaching an HbA1c target of below 6.5%. This suggests a potential significant benefit for patients with type 2 diabetes in managing their blood glucose.
- Safety Profile: The safety profile of orforglipron appeared consistent with other GLP-1 receptor agonists. The most frequently reported adverse events were mild to moderate gastrointestinal issues (diarrhea, nausea, dyspepsia, constipation, vomiting), primarily occurring during dose escalation. No serious adverse events or signals of liver toxicity were observed. The drug discontinuation rate ranged from 10% to 17%.
Significance and Outlook of Oral GLP-1 Obesity Drugs
Currently, the obesity treatment market is dominated by injectable GLP-1 receptor agonists such as semaglutide (Saxenda, Wegovy) and tirzepatide (Mounjaro, Zepbound). While these injectables have demonstrated significant weight loss efficacy, their administration method presents a barrier for some patients.
The Phase 3 success of orforglipron is highly significant as it unlocks the potential for an oral treatment option that can greatly enhance patient convenience. A once-daily pill that can be taken without regard to meals could provide a new avenue for patients who are hesitant about or averse to injections, potentially encouraging more individuals with obesity to seek treatment.
Based on these Phase 3 results, Eli Lilly intends to submit a New Drug Application (NDA) to the U.S. FDA for obesity treatment by the end of 2025, with plans to follow with a submission for type 2 diabetes in 2026. If approved, orforglipron would position Eli Lilly with a robust portfolio of both injectable and oral obesity treatments, potentially reshaping the competitive landscape of the obesity market.
However, the development of oral GLP-1 therapies has faced considerable challenges. Other pharmaceutical companies, including Amgen and Pfizer, have previously pursued oral obesity drugs but encountered setbacks, including trial discontinuations. Eli Lilly's success with orforglipron in overcoming these technical hurdles and reaching Phase 3 completion is particularly noteworthy.
The future approval and launch of orforglipron, along with the accumulation of real-world efficacy and safety data, is expected to usher in a significant era for oral obesity medications. This development holds promising prospects for the many individuals worldwide who are affected by obesity.