The FDA has expedited approval for Eli Lilly’s new weight-loss pill, which works like widely used injectable medications to mimic a natural hormone that controls appetite and feelings of fullness, reports The Associated Press. It follows on Novo Nordisk’s recently released oral Wegovy pill, approved in December.
The GLP-1 drug orforglipron – branded as Foundayo – was expected to begin shipping this week.
The FDA authorised Lilly’s drug as part of a new programme aimed at cutting drug approval times, and said it reviewed the company’s application in just 50 days.
In a clinical trial of more than 3 000 obese adults, participants who received the highest dose of orforglipron, 36 milligrams, lost 11.2% of their body weight over more than 16 months. That compared with a 2.1% weight loss in patients who received a placebo, or dummy pill, according to The New England Journal of Medicine.
Both the Lilly and Novo Nordisk pills resulted in less weight loss than the average achieved with Lilly’s injectable Zepbound, which results in a 21% average weight loss, or Novo Nordisk’s injectable Wegovy, which averages about 15%.
Both once-daily pills promise convenience, but orforglipron is a small-molecule GLP-1 drug that can be taken without restrictions. The Wegovy pill, a peptide, must be taken with a sip of water in the morning on an empty stomach, with a 30-minute wait before eating or drinking.
Users of orforglipron also saw improvements in waist circumference, blood pressure, triglyceride levels and cholesterol levels, the study found.
Side effects, mostly gastrointestinal issues, led to between 5% and 10% of participants in the orforglipron study discontinuing treatment, compared with nearly 3% in the placebo group.
About one in eight people in the US have used injectable GLP-1 drugs, according to a survey from KFF, a non-profit health policy research group. But many more have trouble affording the costly shots.
Study details
Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment
Sean Wharton, Louis Aronne, Adam Stefanski et al.
Published in The New England Journal of Medicine on 16 September 2025
Abstract
Background
Orforglipron, a small-molecule, nonpeptide oral glucagon-like peptide-1 (GLP-1) receptor agonist, is being investigated as a treatment for obesity.
Methods
In this phase 3, multinational, randomised, double-blind trial, we examined the safety and efficacy of once-daily orforglipron at doses of 6 mg, 12 mg, or 36 mg, as compared with placebo (assigned in a 3:3:3:4 ratio) as an adjunct to healthy diet and physical activity for 72 weeks. All the patients had obesity without diabetes mellitus. The primary end point was the percent change in body weight from baseline to week 72, as assessed according to the treatment-regimen estimand in the intention-to-treat population.
Results
A total of 3127 patients underwent randomisation. The mean change in body weight from baseline to week 72 was −7.5% (95% confidence interval [CI], −8.2 to −6.8) with 6 mg of orforglipron, −8.4% (95% CI, −9.1 to −7.7) with 12 mg of orforglipron, and −11.2% (95% CI, −12.0 to −10.4) with 36 mg of orforglipron, as compared with −2.1% (95% CI, −2.8 to −1.4) with placebo (P<0.001 for all comparisons with placebo). Among the patients in the orforglipron 36-mg group, 54.6% had a reduction of 10% or more, 36.0% had a reduction of 15% or more, and 18.4% had a reduction of 20% or more, as compared with 12.9%, 5.9%, and 2.8% of the patients, respectively, in the placebo group. Waist circumference, systolic blood pressure, triglyceride levels, and non-HDL cholesterol levels significantly improved with orforglipron treatment as compared with placebo. Adverse events resulted in treatment discontinuation in 5.3 to 10.3% of the patients in the orforglipron groups and in 2.7% of those in the placebo group. The most common adverse events with orforglipron were gastrointestinal effects, which were mostly mild to moderate.
Conclusions
In adults with obesity, 72-week treatment with orforglipron led to significantly greater reductions in body weight than placebo; the adverse-event profile was consistent with that of other GLP-1 receptor agonists.
The Associated Press article – FDA grants to Eli Lilly’s weight-loss pill for obesity (Open access)
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