OASIS 4 trial results showed average weight loss of 13.6% with a daily 25 mg semaglutide tablet, versus 2.2% with placebo, a pill without active medicine. Those were the results at 64 weeks. The often quoted 16.6% answers a different question: what would happen if everyone continued treatment.
Neither predicts what one person will lose, or establishes the results of a compounded preparation.
What the Wegovy pill trial asked
Could a daily 25 mg tablet help adults lose more weight than placebo when both groups received support with eating and movement?
That was the question Sean Wharton and colleagues tested in OASIS 4, published in the New England Journal of Medicine in 2025. Novo Nordisk funded the study. It tested the manufacturer's oral formulation, rather than an injection.
Who took part, and for how long?
The study assigned 307 adults by chance: 205 to semaglutide and 102 to placebo. Neither participants nor the treating study staff knew which tablet someone received.
The trial registry, NCT05564117, lists adults aged 18 or older with obesity, or overweight and a related condition. Entry required a BMI of at least 30, or at least 27 with a condition such as high blood pressure. BMI is weight relative to height.
Diabetes was excluded at screening. So were recent weight changes exceeding 5 kilograms, about 11 pounds. The average age was 48; about four in five participants were women, and about nine in ten were White.
Treatment lasted 64 weeks, including 12 weeks of gradual dose increases, followed by seven weeks off treatment. Follow-up after random assignment therefore ran 71 weeks. Both groups received counseling on diet and physical activity.
What the researchers measured
The primary endpoints, the main outcomes researchers planned to measure, were percentage weight change and the proportion losing at least 5%. Both were assessed at week 64. Higher weight-loss thresholds and a questionnaire about physical functioning were also measured.
OASIS 4 trial results: why there are two averages
An estimand defines the treatment effect a study aims to measure, including how it handles people stopping treatment. OASIS 4 used two.
Treatment policy included treatment stops and additional weight-loss treatments. Trial product estimated what would happen if everyone continued assigned treatment without those additional treatments. The second uses a mathematical model; it isn't simply an average of people who finished.
| Analysis at week 64 | Oral semaglutide 25 mg | Placebo |
|---|---|---|
| Treatment policy: includes treatment changes | 13.6% weight loss | 2.2% weight loss |
| Trial product: assumes continued treatment | 16.6% weight loss | 2.7% weight loss |
The paper's main comparison was an 11.4 percentage-point difference, meaning the gap between 13.6% and 2.2%. Our estimand guide explains the distinction further.
The paper also reported these observed proportions among people with week-64 weight measurements: 192 in the tablet group and 90 receiving placebo.
| Weight lost from the starting weight | Tablet group | Placebo group |
|---|---|---|
| At least 5% | 79.2% | 31.1% |
| At least 10% | 63.0% | 14.4% |
| At least 15% | 50.0% | 5.6% |
| At least 20% | 29.7% | 3.3% |
About half of that measured tablet group lost at least 15%. These observed proportions use available weights; they are different from model-based estimates that account for missing measurements.
What side effects were reported?
About three in four tablet participants reported gastrointestinal events, meaning stomach or bowel problems: 74.0%, versus 42.2% with placebo. A pill avoided needles, but it did not avoid digestive effects.
The OASIS 4 publication and its registry reported:
| Reported event | Oral semaglutide | Placebo |
|---|---|---|
| Any stomach or bowel event | 74.0% | 42.2% |
| Nausea | 46.6% | 18.6% |
| Vomiting | 30.9% | 5.9% |
| Constipation | 20.1% | 9.8% |
| Diarrhea | 17.6% | 8.8% |
| Stopped treatment because of a medical event | 6.9% | 5.9% |
The safety analysis counted 204 tablet users and 102 placebo users who received at least one dose. A reported event doesn't automatically establish that the medicine caused it. A study this size also cannot settle every question about rare harms.
The tablet's dosing conditions matter
As of September 30, 2026, the day this article was written, the current Wegovy label on DailyMed carries “Revised: 6/2026.” Its tablet conditions are specific: an empty stomach in the morning, up to 4 ounces of plain water, and the tablet swallowed whole. The label requires at least 30 minutes before food, other drinks or other oral medicines. The prescriber sets the actual dose.
Those conditions affect absorption, how much medicine reaches the blood. In Bækdal and colleagues' two dosing studies, Diabetes Therapy, 2021, eating before the tablet left limited or no measurable medicine in the blood. Longer waits before eating increased the amount absorbed.
The tablet includes an absorption enhancer, an ingredient helping semaglutide cross the stomach lining. Our oral semaglutide guide covers that delivery system.
What later research adds, and leaves open
The earlier OASIS 1 trial, Knop and colleagues, The Lancet, 2023, tested 50 mg daily and reported 15.1% weight loss versus 2.4% at 68 weeks; it did not directly compare that dose with OASIS 4's 25 mg.
As of September 30, 2026, the day this article was written, a June 1, 2026 analysis by Plotkin and colleagues suggested comparable weight outcomes for the 25 mg tablet and weekly 2.4 mg injections. It compared separate trials, rather than assigning people directly between the two forms. The authors acknowledged differences in geography and study conduct; safety outcomes were not formally compared. Novo funded that analysis too.
In an August 20, 2026 letter in Postgraduate Medicine, Yi Zou argued that similar averages across separate trials don't establish that pills and injections perform the same. Daily routines and treatment continuation also matter.
What recent pill headlines add
As of September 30, 2026, the day this article was written, Novo announced OCTANE results: 194 selected injection users who switched and remained on the pill lost an average 4.1% after three months. There was no group continuing injections. Our switching-to-Wegovy-pill guide covers that separate question.
Lilly's September 29, 2026 announcement reported greater weight loss with orforglipron, using separate diabetes trials. That indirect comparison didn't test the medicines together at those doses. It doesn't replace OASIS 4's obesity evidence. The orforglipron guide explains that different pill.
What this means for a compounded prescription
Compounding means a pharmacy prepares medicine for a particular prescription. Semaglutide and tirzepatide prescribed through Promise are dispensed by a licensed U.S. compounding pharmacy as compounded medications, which are different from FDA-approved products: the formulations offered here are not FDA-approved.
As of September 30, 2026, the day this article was written, the FDA's explanation, marked “Content current as of: 09/01/2026”, states that compounded drugs do not undergo its review for safety, effectiveness or quality before marketing. A licensed provider may still prescribe a compounded formulation; that decision is between the patient and the doctor.
Tirzepatide acts on GLP-1, a gut-hormone signal involved in fullness and blood sugar, and GIP, a second gut-hormone signal. OASIS 4 did not compare tirzepatide with the tablet. It also cannot establish equivalent outcomes for a compounded preparation.
What belongs in the visit
The useful discussion includes medical history, other medicines, digestive tolerability and whether a daily fasting routine is practical. The study's average belongs alongside those questions.
At Promise, a licensed provider reviews every request and prescribes only when medically appropriate; not everyone qualifies.
