What the trial found
OASIS 4 was a 64-week, randomised, double-blind, placebo-controlled trial conducted across 22 sites in four countries.1
The researchers enrolled 307 adults without type 2 diabetes who had a BMI of 30 or above, or a BMI of 27 or above with at least one weight-related condition.
Participants were randomly assigned in a 2:1 ratio to receive either oral semaglutide 25 mg or a placebo once a day, alongside lifestyle changes.
The key results:
- 13.6% average weight loss with oral semaglutide, compared to 2.2% with placebo
- 76.3% of people on the pill achieved at least 5% weight loss, compared to 31.3% on placebo
- 55.6% achieved at least 10% weight loss
- Around 30% achieved 20% or more weight loss
There’s an important distinction in how these results are reported. The 13.6% figure represents the intention-to-treat analysis, which includes everyone who started the trial regardless of whether they completed it or took every dose.
Among participants who fully adhered to treatment for 64 weeks, the average weight loss was 16.6%.1
The intention-to-treat number tells you what to expect across a broad population. The adherence figure tells you what’s possible if you take the medication consistently.
Beyond weight loss, the trial also found improvements in physical function. People taking oral semaglutide reported significantly better quality-of-life scores on a measure of the physical impact of their weight.1
How the pill compares to injectable Wegovy
The OASIS 4 results are closely aligned with those from the major injectable semaglutide trials.
The STEP 1 trial found that injectable Wegovy 2.4 mg (given weekly) produced an average weight loss of 14.9% over 68 weeks.2
The difference between that and the pill’s 13.6% over 64 weeks is small, and the trials weren’t designed as a head-to-head comparison, so a direct comparison isn’t appropriate.
The more recently approved injectable dose, Wegovy 7.2 mg, produced an average of 20.7% weight loss over 72 weeks in the STEP UP trial. That’s a meaningful step above what the pill achieved, but it’s also a much higher dose with a longer escalation period.
A separate trial, OASIS 1, tested a 50 mg oral dose and reported an average weight loss of around 15.1%.4
This higher oral dose isn’t approved, but the data suggest that the ceiling of oral semaglutide may still be higher than what OASIS 4 demonstrated.
How oral semaglutide works differently
Getting oral GLP-1 medications to work is challenging because semaglutide is a large peptide, and peptides are normally broken down by stomach acid and digestive enzymes before they reach the bloodstream.
The solution is SNAC (salcaprozate sodium), an absorption enhancer that’s included in every Wegovy tablet.5
SNAC works by temporarily raising the pH around the tablet in the stomach, thereby protecting semaglutide from acid degradation.
It also increases absorption through the stomach lining, allowing enough semaglutide to enter the bloodstream to produce a therapeutic effect.5
This absorption issue is why the dosing instructions are so specific. The tablet must be taken on an empty stomach with no more than 120 ml of plain water, and you need to wait at least 30 minutes before eating, drinking, or taking other medications.
Food, larger volumes of water, or other liquids in the stomach significantly reduce absorption. If the tablet isn’t taken correctly, the medication may not reach effective levels.
The injection bypasses the digestive system entirely, which is why it only needs to be given once a week. The pill has to survive the stomach, which requires daily dosing and a strict fasting routine.
Side effects and safety
The side effect profile in OASIS 4 was consistent with what we’ve seen in injectable semaglutide trials.
The most common side effects were gastrointestinal: nausea, diarrhoea, and vomiting, which occurred most frequently during the dose-escalation phase and were generally rated as mild to moderate.1
Serious adverse events were less common with oral semaglutide (3.9%) than with placebo (8.8%).1 This is consistent with the broader safety profile of semaglutide across multiple trials, though it’s worth noting the relatively small sample size.
The Wegovy pill carries the same boxed warning as the injection regarding thyroid C-cell tumours observed in animal studies.
This risk hasn’t been confirmed in humans, but the medication isn’t recommended for anyone with a personal or family history of medullary thyroid carcinoma.
Post-hoc analyses from the trial also showed improvements in cardiometabolic risk factors, including blood pressure, cholesterol, and C-reactive protein. Among participants who had prediabetes at baseline, over 70% achieved normal blood glucose levels by week 64.1
Limitations to keep in mind
OASIS 4 is a well-designed trial, but there are several limitations worth noting.
The sample size was relatively small at 307 participants. In comparison, the major injectable semaglutide trials enrolled thousands of participants.
Larger trials provide more statistical power and are better at detecting rarer side effects or identifying which patient subgroups respond best.
The trial excluded people with type 2 diabetes. Since a significant proportion of people with obesity also have type 2 diabetes, the results may not fully reflect what would happen in that population.
The participant group was predominantly white (92%) and female (79%).1 So, it’s unclear whether the results can be generalisable to the broader population.
The trial lasted 64 weeks, which is enough to demonstrate meaningful weight loss, but it doesn’t tell us about long-term durability.
Whether people maintain their weight loss on the pill over two, three, or five years remains to be seen.
Finally, the 25 mg dose tested in OASIS 4 is only one of the oral doses being studied.
OASIS 1 tested 50 mg and found greater weight loss,4 raising the question of whether the currently approved dose represents the optimal balance of efficacy and tolerability.
What this means for the UK
The Wegovy pill is currently only available in the US, where it launched in January 2026.
Novo Nordisk submitted oral semaglutide 25 mg to the European Medicines Agency and the MHRA during the second half of 2025.3
Based on typical regulatory timelines, UK approval could come in late 2026, with private providers likely to offer it before NHS access is established.
For people already taking injectable Wegovy or Mounjaro in the UK, the pill doesn’t change anything right now. But it does expand the options available in the coming months.
For people who have considered GLP-1 treatment but haven’t started because of needle aversion, the OASIS 4 data provide evidence that a pill alternative can deliver comparable results.
For a practical overview of the Wegovy pill, including dosing, how to take it, and a comparison table, see our full guide: The Wegovy pill: what it is, how it works, and when it’s coming to the UK.
Take home message
The OASIS 4 trial demonstrates that oral semaglutide 25 mg produces weight loss comparable to the 2.4 mg injectable dose of Wegovy.
For the first time, people who are unable or unwilling to inject have a GLP-1 option for weight management backed by a rigorous, placebo-controlled trial published in the New England Journal of Medicine.
The pill isn’t yet available in the UK, but regulatory review is underway, and approval is expected in late 2026.
Regardless of how the medication is delivered, the evidence consistently shows that combining GLP-1 treatment with structured lifestyle support improves long-term outcomes.
Second Nature’s published research found that members taking semaglutide alongside dietitian-led behaviour change support achieved an average of 19.1% weight loss at 12 months.6
Second Nature's Mounjaro and Wegovy programmes
Second Nature provides Mounjaro or Wegovy as part of our Mounjaro and Wegovy weight-loss programmes.
Why choose Second Nature over other medication providers, assuming you're eligible?
Because peace of mind matters.
We've had the privilege of working with the NHS for over eight years, helping people across the UK take meaningful steps toward a healthier, happier life.
Our programmes are designed to meet people where they are, whether that means support with weight loss through compassionate one-to-one health coaching, or access to the latest weight-loss medications (like Mounjaro and Wegovy) delivered alongside expert care from a multidisciplinary team of doctors, psychologists, dietitians, and personal trainers.
At the heart of everything we do is a simple belief: real, lasting change comes from building better habits, not relying on quick fixes. We're here to support that change every step of the way.
With over a decade of experience, thousands of lives changed, and a long-standing record of delivering programmes used by the NHS, we believe we're the UK's most trusted weight-loss programme.
We hope to offer you something invaluable: peace of mind, and the support you need to take that first step.
References
- Wharton, S., et al. (2025). Oral semaglutide at a dose of 25 mg in adults with overweight or obesity. New England Journal of Medicine, 393(11).
- Wilding, J.P., et al. (2021). Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine, 384(11), 989-1002.
- Novo Nordisk. (2025). Wegovy pill approved in the US as first oral GLP-1 for weight management. Press release, 22 December 2025.
- Knop, F.K., et al. (2023). Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1). The Lancet, 402(10403), 705-719.
- Buckley, S.T., et al. (2018). Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist. Science Translational Medicine, 10(467).
- Richards, R., et al. (2025). A remotely delivered, semaglutide-supported specialist weight management program: 12-month outcomes. JMIR Formative Research, 9(1), e72577.
