- In ATTAIN-1, adults with obesity and without diabetes who took the highest dose of orforglipron (Foundayo) lost 11.2% of their body weight on average over 72 weeks, vs 2.1% on placebo.1
- In ATTAIN-2, adults with type 2 diabetes lost 9.6% on the highest dose, vs 2.5% on placebo.2
- The FDA approved it as Foundayo on April 1, 2026. Stomach and gut side effects were common, mostly mild to moderate, and most frequent while the dose was being raised.3
What is orforglipron?
Orforglipron is a GLP-1 receptor agonist made by Eli Lilly. Unlike semaglutide or tirzepatide, it is not a peptide. It is a small molecule, closer to a conventional pill, and it is taken once a day by mouth. The FDA label says there is no clinically relevant effect of food on how much of the medicine is absorbed.3
The FDA approved it under the brand name Foundayo on April 1, 2026.3 It is approved, with a reduced-calorie diet and more physical activity, for adults with obesity, or adults with overweight plus at least one weight-related condition. The label says it should not be combined with another GLP-1 medicine.
How much weight did people lose in ATTAIN-1?
ATTAIN-1 was the main trial for weight management. It enrolled 3,127 adults with obesity and without diabetes and ran for 72 weeks. People were randomly assigned to one of three orforglipron doses or a placebo, and everyone got advice on diet and activity.1
These averages include everyone assigned to a group, whether or not they kept taking the pill. On the highest dose, more people reached bigger milestones:1
| Weight lost at week 72 | Orforglipron 36 mg | Placebo |
|---|---|---|
| 10% or more | 54.6% | 12.9% |
| 15% or more | 36.0% | 5.9% |
| 20% or more | 18.4% | 2.8% |
Waist size, systolic blood pressure, triglycerides and non-HDL cholesterol also improved more than on placebo.1
What about people with type 2 diabetes?
ATTAIN-2 enrolled 1,613 adults with type 2 diabetes and a BMI of 27 or higher, also for 72 weeks.2 Average weight change was −5.1%, −7.0% and −9.6% on the three doses, vs −2.5% on placebo. Blood sugar (HbA1c) also improved. People with diabetes usually lose less weight on GLP-1 medicines than people without it, a pattern we cover in GLP-1 weight loss with type 2 diabetes.
What are the side effects of orforglipron?
Like other GLP-1 medicines, the most common side effects were in the stomach and gut. The FDA label pools the two weight-loss trials:3
| Side effect | Placebo | Foundayo 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% |
| Stopped treatment due to side effects | 3% | 6% | 9% | 10% |
The label says nausea, vomiting and diarrhea were more common while the dose was being raised and decreased over time. Hair loss was reported by 4% to 5% on Foundayo vs 2% on placebo.3 In ATTAIN-2, low blood sugar (below 54 mg/dL) was reported in 2% of people on Foundayo vs 0.2% on placebo, and it was more common in people also taking a sulfonylurea.3
Foundayo carries a boxed warning about thyroid C-cell tumors, like other GLP-1 medicines. The label notes that orforglipron did not cause tumors in rats or mice, but that it is not active in those animals, so the human relevance is not known. It should not be used by people with a personal or family history of medullary thyroid cancer or MEN 2.3 See also our guides to GLP-1 nausea and GLP-1s and thyroid cancer.
Orforglipron vs oral semaglutide
For weight loss in people without diabetes, no published trial has compared the two pills directly. Separate trials show similar ranges: in OASIS 4, daily oral semaglutide 25 mg led to 13.6% average loss at 64 weeks, vs 11.2% at 72 weeks for orforglipron 36 mg in ATTAIN-1.8,1 Details are in our oral semaglutide article.
Two other pieces of evidence exist, and both need context:
- ACHIEVE-3 (type 2 diabetes, head to head). In 1,698 adults with type 2 diabetes, orforglipron lowered HbA1c more than oral semaglutide over 52 weeks (−1.91% on 36 mg vs −1.47% on semaglutide 14 mg). Stomach and gut side effects were more frequent with orforglipron (58% to 59% vs 37% to 45%), as were stops due to side effects (9% to 10% vs 4% to 5%).4 This was an open-label trial funded by Lilly, and its main outcome was blood sugar, not weight.
- An indirect comparison funded by Novo Nordisk. Using OASIS 4 and ATTAIN-1 data, it estimated about 3 percentage points more weight loss with oral semaglutide 25 mg than with orforglipron 36 mg, and more stops due to side effects with orforglipron.6 Indirect comparisons rely on statistical adjustment and are weaker than a head-to-head trial.
Orforglipron vs tirzepatide (Zepbound)
No trial has compared orforglipron with tirzepatide (Zepbound, Mounjaro) for weight loss. In SURMOUNT-1, a separate 72-week trial in adults with obesity and without diabetes, weekly tirzepatide 15 mg led to an average loss of 20.9%, vs 3.1% on placebo.7 That is larger than the 11.2% in ATTAIN-1, but different trials enrolled different people, so this is context, not a ranking.
One trial looked at switching. ATTAIN-MAINTAIN took people who had already lost weight on tirzepatide or semaglutide injections and moved them to orforglipron or placebo for 52 weeks.5 Among people who came from tirzepatide, those on orforglipron kept an estimated 74.7% of their earlier weight loss, vs 49.2% on placebo. Among those who came from semaglutide, the figures were 79.3% vs 37.6%. The trial had no group that stayed on the injection, so it cannot say how switching compares with continuing. For what usually happens after stopping, see weight regain after stopping a GLP-1.
Reading these results
- Who was studied. Adults with obesity, or overweight with a weight-related condition. ATTAIN-1 excluded diabetes; ATTAIN-2 required it.
- Who paid. All the orforglipron trials here were funded by Lilly. The indirect comparison was funded by Novo Nordisk, which makes semaglutide.
- Averages hide a wide range. In ATTAIN-1, about 1 in 5 people on the top dose lost 20% or more, while many lost less than 10%.
Whether a daily pill, a weekly injection or neither suits you depends on your health, other medicines, cost and access. That is a decision to make with your prescriber.
Common questions
How much weight do people lose on orforglipron (Foundayo)?
In the ATTAIN-1 trial of 3,127 adults with obesity and without diabetes, people on the highest dose of orforglipron lost 11.2% of their body weight on average over 72 weeks, compared with 2.1% on placebo. In ATTAIN-2, in adults with type 2 diabetes, the highest dose led to an average loss of 9.6% vs 2.5% on placebo.
What are the side effects of orforglipron?
The most common side effects are in the stomach and gut. In the FDA label's pooled data from the two weight-loss trials, nausea was reported by 26% to 35% of people on Foundayo depending on dose, vs 10% on placebo, and 6% to 10% stopped treatment because of side effects, vs 3% on placebo.
Is orforglipron FDA approved?
Yes. The FDA approved orforglipron under the brand name Foundayo on April 1, 2026, for adults with obesity, or with overweight plus at least one weight-related condition, alongside a reduced-calorie diet and more physical activity.
Is orforglipron better than tirzepatide (Zepbound)?
No trial has compared them head to head for weight loss. In separate trials, the highest orforglipron dose led to 11.2% average weight loss at 72 weeks in ATTAIN-1, while tirzepatide 15 mg led to 20.9% at 72 weeks in SURMOUNT-1, but the trials enrolled different people and cannot be compared directly.
Sources
- Wharton S, Aronne LJ, Stefanski A, et al. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment (ATTAIN-1). N Engl J Med. 2025;393(18):1796-1806. PubMed · doi:10.1056/NEJMoa2511774
- Horn DB, Ryan DH, Kis SG, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. Lancet. 2026;406(10522):2927-2944. PubMed · doi:10.1016/S0140-6736(25)02165-8
- U.S. Food and Drug Administration. FOUNDAYO (orforglipron) tablets: prescribing information and approval letter, NDA 220934, approved April 1, 2026. Prescribing information (Aug 2026) · Approval letter
- Rosenstock J, Yabe D, Cox D, et al. Efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes (ACHIEVE-3): a multinational, multicentre, non-inferiority, open-label, randomised, phase 3 trial. Lancet. 2026;407(10534):1147-1160. PubMed · doi:10.1016/S0140-6736(26)00202-3
- Aronne LJ, Horn DB, le Roux CW, et al. Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial. Nat Med. 2026;32(7):2679-2687. PubMed · Full text (PMC)
- Michalak W, Bøg M, Bendixen T, et al. Oral Semaglutide 25 mg Versus Orforglipron 36 mg in Obesity: A Population-Adjusted Indirect Treatment Comparison. Diabetes Obes Metab. 2026;28(8):7247-7256. PubMed · Full text (PMC)
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022;387(3):205-216. PubMed · doi:10.1056/NEJMoa2206038
- Wharton S, Lingvay I, Bogdanski P, et al. Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity (OASIS 4). N Engl J Med. 2025;393(11):1077-1087. PubMed · doi:10.1056/NEJMoa2500969
