Eli Lilly reported that its investigational oral agent, orforglipron, achieved body weight reductions of up to 7.9% and lowered HbA1c in adults with type 2 diabetes in a phase III trial.

The once-daily GLP-1 receptor agonist was associated with mean weight loss of 4.7% at 3 mg, 6.1% at 12 mg, and 7.9% at 36 mg after 40 weeks. Participants receiving placebo lost 1.6%. HbA1c levels decreased by a mean of 1.3% to 1.6% across treatment groups.

Discontinuation rates were 8% at the highest dose, with gastrointestinal adverse events reported across all groups. Nausea occurred in 13% to 18% of orforglipron-treated patients (vs 2% placebo), diarrhea in 19% to 26%, and vomiting in 5% to 14%. No liver safety signals were observed.

Lilly stated it plans to submit global regulatory filings by year-end and has begun stockpiling the drug.

Unlike injectable GLP-1 receptor agonists—such as tirzepatide (Mounjaro, Zepbound), semaglutide (Ozempic, Wegovy), and other peptide-based agents—orforglipron is a non-peptide small molecule designed to activate the GLP-1 receptor.

If approved, oral small-molecule GLP-1 agents could expand access and simplify manufacturing and distribution compared to peptide-based therapies.

Pfizer discontinued development of its GLP-1 pill candidate danuglipron earlier this week following a case of suspected drug-induced liver injury.