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Lilly eyes FDA review after oral GLP-1 weight loss trial

Eli Lilly's daily oral GLP-1, orforglipron, led to weight loss and improved glycemic control in a Phase 3 trial, setting it up for FDA review and competition with oral Wegovy.

Alivia Kaylor, MSc
By
Published: 27 Aug 2025

Yesterday, Eli Lilly announced positive weight loss results from a phase 3 trial in adults with obesity and type 2 diabetes, indicating that the company now has the necessary clinical data to apply for FDA approval of its daily oral GLP-1 receptor agonist, orforglipron.

Although Novo Nordisk's pill version of semaglutide (Wegovy) is still on track to become the first oral GLP-1 receptor agonist (RA) for weight loss, orforglipron could achieve more commercial success, if approved, despite underperforming clinical results.

Clinical results

In the phase 3 ATTAIN-2 trial, participants with obesity or overweight and type 2 diabetes were randomly administered 6, 12 or 36 milligrams (mg) of orforglipron or a placebo daily for 72 weeks.

All doses achieved statistically significant and clinically meaningful weight loss.

Compared to the placebo, people taking the highest dose (36 mg) lost an average of 22.9 lbs (10.5%) of body weight, while those administered 6 and 12 mg achieved 6% and 8% reductions, respectively.

The clinical results also showed that participants given the highest dosage reached weight loss thresholds of 10% and 15% of their body weight at higher rates than the placebo groups. Nearly half (45.6%) of the participants achieved at least 10% weight loss after taking the highest dose, and more than a quarter (26.0%) reached 15% or greater.

In addition to weight loss, orforglipron improved glycemic control. Hemoglobin A1C levels decreased by an average of 1.8% in the highest dose group, with 75% of participants achieving an A1C of 6.5% or lower, compared with just 10.6% in the placebo group.

However, discontinuation rates influenced by side effects of around 10% in the highest dose group, compared to 5% in the placebo group, raise real-world tolerability concerns.

Industry competition

In May, the FDA accepted Novo Nordisk's New Drug Application for its once-daily oral formulation of Wegovy and is expected to announce a decision before the end of the year.

Based on OASIS 4 trial data, adults with obesity or overweight and at least one comorbidity who received 25 mg of oral Wegovy once daily lost an average of 15.1% of their body weight over 64 weeks, compared with 2.4% for placebo. Nearly two-thirds of participants (67.8%) achieved at least 10% weight loss, while 44.2% reached 15% or greater.

Although Novo Nordisk's oral version of Wegovy resulted in greater weight loss than Eli Lilly's orforglipron, the Phase 2 OASIS trial excluded individuals with diabetes.

If approved for weight loss, orforglipron's diabetes data could support future label expansions, giving Eli Lilly a potential competitive edge and distinct commercial niche.

Oral GLP-1 RAs entering the market with FDA approval will mark a new competitive phase for diabetes and anti-obesity treatments, particularly for those hesitant to start injectables. But observing how patients tolerate the therapy outside clinical trials will be key to determining their commercial success.

Alivia Kaylor is a scientist and the senior site editor of Pharma Life Sciences.

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