Orforglipron
A once-daily GLP-1 tablet, and a small molecule rather than a peptide. Its 72-week phase 3 trial in 3,127 adults measured weight loss against placebo, not against the injected drugs.
- U.S. status
- FDA-approved
- Foundayo (orforglipron) tablets, NDA 220934, approved April 1, 2026 for chronic weight management.
- FDA source, read September 2026.
- Evidence cited here
- Weight: Large trials1 randomized trial of 1,000 or more people cited here for weight.
- Forms sold
- Oral
1. What Orforglipron is
Orforglipron activates the GLP-1 receptor, the same target as semaglutide and tirzepatide, but it is not a peptide. It is a small, nonpeptide molecule taken as a tablet once a day. The FDA approved it in April 2026 as Foundayo for chronic weight management.
It is covered here because it acts on the same receptor as the GLP-1 peptides and readers weigh it against them. Only Foundayo is FDA-approved; a compounded preparation sold under the name is not, and neither trial below tested one.
2. How it works
Peptide drugs are mostly broken down in the gut, which is why nearly all GLP-1 drugs are injections. Orforglipron is a different kind of molecule that is absorbed from a swallowed tablet, then slows stomach emptying and reduces appetite through the GLP-1 receptor.
The dose is raised in steps. In both trials, stomach side effects were the most common, mostly mild to moderate, and in the phase 2 trial they occurred mainly while the dose was rising.
3. What the studies measured
ATTAIN-1 randomized 3,127 adults with obesity, without diabetes, to 6, 12 or 36 mg a day or placebo for 72 weeks, alongside diet and activity advice. Weight fell 7.5%, 8.4% and 11.2% on the three doses, against 2.1% on placebo.
On 36 mg, 54.6% lost at least 10% of their weight, against 12.9% on placebo. Adverse events led 5.3% to 10.3% of the orforglipron groups to stop, against 2.7% on placebo.
The earlier phase 2 trial randomized 272 adults to one of four doses from 12 to 45 mg, or placebo. At 36 weeks, weight fell 9.4% to 14.7% across doses against 2.3% on placebo; stomach side effects led 10% to 17% to stop.
4. What they did not measure
Both trials compared orforglipron with placebo, not with an injected GLP-1 drug. Neither measured how it compares with semaglutide or tirzepatide in the same people.
Neither trial followed people after they stopped taking it, and neither measured heart attacks or strokes. Approved in 2026, it has a short record outside clinical trials.
The studies behind this page
The evidence label above is computed from these papers: their design and how many people they enrolled.
- Randomized trial
3,127 people
Counts toward: Weight
Mean weight change of −7.5%, −8.4% and −11.2% by dose, against −2.1% on placebo.
Adults with obesity, without diabetes; orforglipron 6, 12 or 36 mg daily or placebo for 72 weeks (ATTAIN-1).
Wharton S, Aronne LJ, Stefanski A, Alfaris NF, Ciudin A, Yokote K, et al. (2025). Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. N Engl J Med. PMID 40960239
- Randomized trial
272 people
Counts toward: Weight
Mean weight change of −9.4% to −14.7% across doses at week 36, against −2.3% on placebo.
Adults with obesity, or overweight with a weight-related condition, without diabetes; 12, 24, 36 or 45 mg daily or placebo for 36 weeks (phase 2).
Wharton S, Blevins T, Connery L, Rosenstock J, Raha S, Liu R, et al. (2023). Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. N Engl J Med. PMID 37351564
Orforglipron
Frequently asked questions
- Is orforglipron a peptide?
- No. It is a small, nonpeptide molecule that activates the same GLP-1 receptor as semaglutide and tirzepatide, and it is taken as a daily tablet rather than an injection.
- How much weight did people lose on orforglipron?
- In ATTAIN-1, adults on the highest dose, 36 mg a day, lost a mean of 11.2% of their body weight over 72 weeks, against 2.1% on placebo.