Orforglipron, a small-molecule GLP-1 pill

Most GLP-1 receptor agonists on the market were injectable drugs. Eli Lilly's orforglipron was built differently: a small, nonpeptide molecule, taken by mouth once a day, that acts on the same receptor.

Its phase 3 test, ATTAIN-1, randomized 3,127 adults with obesity and without diabetes, in several countries, to 6, 12 or 36 mg of orforglipron or to placebo for 72 weeks, alongside advice on diet and exercise. Mean body weight fell by 7.5%, 8.4% and 11.2% on the three doses and by 2.1% on placebo. Side effects matched those of other GLP-1 receptor agonists. Wharton and colleagues reported the trial in the New England Journal of Medicine in September 2025.

Orforglipron was not the first GLP-1 pill for weight loss. On 22 December 2025 the FDA approved Novo Nordisk's Wegovy pill, oral semaglutide 25 mg once daily, which the company called the first oral GLP-1 receptor agonist approved for weight management; in its OASIS 4 trial, people who kept taking it lost 16.6% of body weight on average. Oral semaglutide is a peptide drug formulated for oral delivery.

The FDA approved Foundayo on 1 April 2026 for adults with obesity, or with overweight and at least one weight-related condition, together with a reduced-calorie diet and more physical activity. Two randomized, double-blind, placebo-controlled trials of 72 weeks supported the decision. Treatment starts at 0.8 mg and rises in steps of at least 30 days, to as much as 17.2 mg. The acting head of the agency's drug center noted that the pill does not need to be taken on an empty stomach. The label warns of pancreatitis, severe gastrointestinal reactions, kidney injury from fluid loss, low blood sugar, gallbladder disease and aspiration under anesthesia, and carries a boxed warning for thyroid C-cell tumors.

It was the fifth approval under the Commissioner's National Priority Voucher pilot program and the first new molecular entity cleared under it. The decision came 50 days after filing, 294 days ahead of its scheduled review date of 20 January 2027.