Every other agent on this site is a peptide. Orforglipron is a small organic molecule that fits the same receptor, which changes almost everything downstream: it is made by chemical synthesis rather than fermentation, it is absorbed like an ordinary tablet, it interacts with liver enzymes the way ordinary drugs do, and it produced no rodent thyroid tumors because it does not activate the rodent receptor at all. It was approved as Foundayo on 1 April 2026.
Mechanism and receptor profile
The Foundayo label describes it as a GLP-1 receptor agonist that binds and activates the human GLP-1 receptor, and notes that GLP-1 receptors are present in brain regions that regulate appetite; in animal studies orforglipron distributed to and activated those neurons. No GIP or glucagon activity. The boxed warning is explicit that orforglipron is not pharmacologically active in rats or mice and did not produce tumors in rodents, but it carries the warning because it is active at the same receptor as the peptides that did.
FDA approval, with dates
| Date | What was approved | Record |
|---|---|---|
| 1 Apr 2026 | New molecular entity: in combination with a reduced-calorie diet and increased physical activity, to reduce excess body weight and maintain weight reduction long term in adults with obesity or adults with overweight plus at least one weight-related condition | NDA 220934, original (letter) |
| 4 Aug 2026 | Labeling revision (current label) | NDA 220934, S-003 |
Six tablet strengths, expressed as base: 0.8, 2.5, 5.5, 9, 14.5 and 17.2 mg.
Dosing as the label states it
- Once daily, with or without food. Swallow whole; do not break, crush or chew. Never more than one tablet a day.
- Start at 0.8 mg. After at least 30 days, increase to 2.5 mg. After at least 30 days on 2.5 mg, increase to 5.5 mg.
- May then increase to the next level (9 mg, 14.5 mg, 17.2 mg) after at least 30 days on the current dose, based on response and tolerability. Maximum 17.2 mg daily.
- Interactions: avoid strong CYP3A4 inhibitors that also inhibit OATP1B; the maximum dose is 9 mg with a strong CYP3A4 inhibitor. Avoid strong CYP3A4 inducers; with moderate inducers, monitor effectiveness and escalate as needed.
That last bullet has no equivalent on any peptide entry. Peptides are broken down by proteases; a small molecule is cleared by the liver's enzyme systems, so common drugs (certain antifungals, antibiotics, anticonvulsants) change its exposure.
Pivotal trials and their numbers
| Trial | Population and duration | Result | PubMed |
|---|---|---|---|
| ATTAIN-1 | 3,127 adults with obesity or overweight, no diabetes; 72 weeks | Weight -7.5% (6 mg), -8.4% (12 mg), -11.2% (36 mg) vs -2.1% placebo; 54.6% on 36 mg lost 10% or more vs 12.9%; discontinuation for adverse events 5.3% to 10.3% vs 2.7% | 40960239 |
| ACHIEVE-1 | 559 adults with early type 2 diabetes on diet and exercise; 40 weeks | HbA1c -1.24, -1.47, -1.48 points (3, 12, 36 mg) vs -0.41 placebo; weight -4.5%, -5.8%, -7.6% vs -1.7% | 40544435 |
| Phase 2 obesity | 272 adults with obesity or overweight; 36 weeks | Weight -9.4% to -14.7% across dose cohorts vs -2.3% placebo; 10% to 17% discontinued for gastrointestinal events | 37351564 |
The phase 2 numbers were larger than the phase 3 numbers, which is common and worth remembering when a new agent's early results are quoted. ATTAIN-1 at 36 mg, minus 11.2%, sits below semaglutide 2.4 mg (STEP 1, minus 14.9%) and the 25 mg semaglutide tablet (OASIS 4, minus 13.6%), across different trials.
Adverse reactions from the label
| Adverse reaction | Placebo % | 5.5 mg % | 9 mg % | 17.2 mg % |
|---|---|---|---|---|
| Nausea | 10 | 26 | 34 | 35 |
| Constipation | 9 | 20 | 27 | 24 |
| Diarrhea | 11 | 21 | 23 | 25 |
| Vomiting | 4 | 13 | 21 | 24 |
| Dyspepsia | 4 | 12 | 16 | 13 |
| Abdominal pain | 7 | 13 | 14 | 14 |
| Headache | 7 | 8 | 9 | 9 |
| Abdominal distension | 3 | 7 | 9 | 8 |
| Fatigue | 4 | 6 | 7 | 9 |
| Eructation | 1 | 6 | 8 | 8 |
| Gastroesophageal reflux disease | 2 | 6 | 6 | 7 |
| Hair loss | 2 | 4 | 4 | 5 |
The profile is the class profile: nausea, constipation, diarrhea and vomiting lead, and rise with dose.
Boxed warning
Risk of thyroid C-cell tumors, worded for a drug that could not be tested in rodents: products with GLP-1 receptor agonist activity that are active in rats and mice caused rodent C-cell tumors; orforglipron is not active in rodents and produced none; the human relevance is unknown. Contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2.
Status and manufacturer
Approved and marketed by Eli Lilly. ACHIEVE trials in type 2 diabetes continue to publish (ACHIEVE-5 with insulin glargine in JAMA, 2026), but no diabetes indication is on the label.
Where next
Compare Foundayo with the 25 mg semaglutide tablet in the comparison table: same route, different molecule class, different rules for taking it. The glossary defines small molecule, peptide and CYP3A4.
Questions people ask
Why are the trial doses (6, 12, 36 mg) different from the Foundayo tablet strengths?
The trials used an investigational formulation. The Foundayo label states that the approved tablets are presented as equivalent dosages of that formulation, so a 36 mg trial dose corresponds to the 17.2 mg Foundayo tablet. Read trial numbers by arm, then map to the label strength.
Can Foundayo be taken with food?
Yes. The label says to take it once daily with or without food, swallowed whole. That is the practical difference from oral semaglutide, which must be taken fasting with a small amount of water and a 30-minute wait.
Is Foundayo approved for diabetes?
No. As of the August 2026 label its only indication is weight reduction and maintenance in adults with obesity or overweight plus a weight-related condition. ACHIEVE-1 showed HbA1c reductions in early type 2 diabetes, but that is not an approved use.
Sources
- Drugs@FDA: NDA 220934 Foundayo (approval 2026-04-01; label supplement 3 approved 2026-08-04) Accessed September 4, 2026.
- FDA approval letter, NDA 220934 (Foundayo), 1 April 2026 Accessed September 4, 2026.
- Foundayo prescribing information, Eli Lilly, DailyMed set id 8ac446c5-feba-474f-a103-23facb9b5c62 Accessed September 4, 2026.
- Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment (ATTAIN-1). N Engl J Med 2025. PubMed 40960239 Accessed September 4, 2026.
- Rosenstock J et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist, in early type 2 diabetes (ACHIEVE-1). N Engl J Med 2025. PubMed 40544435 Accessed September 4, 2026.
- Wharton S et al. Daily oral GLP-1 receptor agonist orforglipron for adults with obesity (phase 2). N Engl J Med 2023. PubMed 37351564 Accessed September 4, 2026.
Canonical URL: https://formblendsglp1s.com/agents/orforglipron. Written by the FormBlends editorial team. This page is educational and is not medical advice; see the medical disclaimer.