Two oral weight loss treatments, two completely different approaches. Orlistat works in your gut, blocking some of the fat you eat from being absorbed. Wegovy semaglutide tablets work through the GLP-1 hormone pathway, reducing your appetite and slowing how quickly your stomach empties.
Both are taken as tablets, but that's roughly where the similarities end. This guide breaks down how each one works, what the evidence shows, who each suits and the key practical differences, so you can make sense of the choice.
Orlistat works on the fat in your food. Wegovy tablets work on your appetite. That difference shapes almost everything else.
What are Wegovy semaglutide tablets?
Wegovy semaglutide tablets contain semaglutide, a GLP-1 receptor agonist. GLP-1 (glucagon-like peptide-1) is a hormone your body naturally makes after eating. It tells your brain you've eaten, reduces your appetite and slows how quickly food leaves your stomach.
By mimicking this hormone, oral semaglutide reduces hunger and cravings, so you feel fuller on smaller portions. That makes it easier to stick to a calorie deficit over time, without the constant hunger that often derails dieting.
Semaglutide has been widely used as an injection for several years. The tablet, branded as Wegovy semaglutide tablets, was approved by the US Food and Drug Administration (FDA) in December 2025, following the phase 3 OASIS 4 trial.
The MHRA approved Wegovy semaglutide tablets on 11 June 2026, making the UK the first country in Europe to license an oral GLP-1 for weight management.
What is orlistat?
Orlistat is a lipase inhibitor. Rather than acting on your brain or appetite, it works locally in your gut.
It attaches to the enzymes (lipases) that break down the fat you eat. That stops roughly a third of that fat being absorbed, which cuts the calories you get from fat in your diet.
Orlistat 120mg has been available in the UK for many years, and is licensed by the MHRA as a prescription-only weight loss treatment. A lower 60mg dose is also available without a prescription, under brand names like Orlos and Alli.
How do they work differently?
The core difference is where each one acts in your body. Orlistat acts in your gut, physically blocking fat absorption. Wegovy tablets act on your brain and digestive system through the GLP-1 pathway, reducing appetite and slowing how quickly your stomach empties.
So they tackle weight from different angles. Orlistat relies on cutting the calories absorbed from fat, which is why it works best alongside a low-fat diet. Wegovy tablets reduce your appetite and how much you eat overall, so they can work with a wider range of eating patterns.
Because they work so differently, they also have different side effects and suitability criteria, which are worth understanding before you choose.
Already eat a fairly low-fat diet? Orlistat has less fat to work on, so ask whether an appetite-based treatment would suit you better.
How effective is each treatment?
Clinical trials give the clearest picture of what each treatment can do.
In the OASIS 4 phase 3 trial, adults taking oral semaglutide 25mg once a day, alongside a reduced-calorie diet and lifestyle support, lost an average of 16.6% of their body weight over 64 weeks if they stuck fully with treatment. Around one in three lost 20% or more.1
Including everyone, whether or not they stayed on treatment, the average was around 13.6%.
For orlistat, the large XENDOS trial found that people taking orlistat 120mg alongside a calorie-restricted diet lost an average of 10.6kg in the first year, compared with 6.2kg in those who dieted without the medicine.2
Both treatments lead to clinically meaningful weight loss when used consistently, alongside healthy lifestyle changes. Oral semaglutide has shown greater average weight loss in trials, though the two haven't been compared head-to-head.
Neither medicine works on its own. Both trials paired treatment with diet and activity changes.
Who is each treatment suitable for?
Wegovy semaglutide tablets
The UK licence covers adults with a BMI of 30 or above, or a BMI of 27 or above with at least one weight-related health condition, such as high blood pressure, high cholesterol or type 2 diabetes.
Wegovy tablets may particularly suit you if you'd prefer a tablet to injections, haven't had enough success with orlistat, or would benefit from the appetite-reducing effects of GLP-1 treatment.
Orlistat
Orlistat 120mg is licensed in the UK for adults with a BMI of 30 or above. You may also be eligible with a BMI of 28 or above if you have related risk factors, like type 2 diabetes, high blood pressure or high cholesterol.3
Orlistat tends to suit people whose diet is fairly high in fat and who want to cut fat absorption directly, or who'd prefer a treatment with a long track record in the UK. You can access it through a consultation at Pharmica without a GP visit.
Do not take either treatment if you're pregnant or breastfeeding. Speak to your GP about other options.
What are the side effects?
Both treatments can cause digestive side effects, but they're quite different.
Wegovy semaglutide tablets
The most common side effects of oral semaglutide are nausea, vomiting, diarrhoea, constipation and tummy discomfort. These tend to be strongest while your dose is going up, as your body adjusts, and usually improve over time.
Starting at a lower dose and increasing gradually helps reduce how often they happen and how bad they are.
Orlistat
Orlistat's side effects come directly from how it works. Because it stops fat being absorbed, the undigested fat passes through your gut. That can cause oily stools, needing the toilet more often, wind and sometimes an urgent need to go, or leakage.
These effects are worse after high-fat meals. Keeping fat below 30% of the calories in each meal significantly lowers the risk.
Orlistat can also reduce how well you absorb the fat-soluble vitamins A, D, E and K. That's why a daily multivitamin, such as OneVit Complete Multivitamin, is recommended alongside orlistat. Take it at bedtime, or at least two hours after your orlistat capsule.3
Severe diarrhoea on orlistat and rely on the pill? Use extra contraception, like condoms, as the pill may not be absorbed properly.
How do you take each treatment?
Orlistat 120mg is taken three times a day, with each main meal. Swallow it whole, just before, during or up to an hour after eating. If you miss a meal, or it contains no fat, you can skip that dose.
Wegovy semaglutide tablets are taken once a day in the morning, on an empty stomach, with no more than a small sip of water. You then have nothing other than water for at least 30 minutes, so the medicine can be absorbed properly.
That's because oral semaglutide uses a technology called SNAC to help it be absorbed through your stomach lining, and SNAC is sensitive to food and other drinks.
Wegovy tablets follow a dose escalation schedule, starting at a lower strength and gradually going up to the 25mg maintenance dose.
Keep your Wegovy tablets by your bed with a small glass of water, so taking one is the first thing you do.
What is the difference in availability?
Orlistat is available now in the UK through Pharmica, after a short clinical consultation. Wegovy semaglutide tablets were approved by the MHRA on 11 June 2026. Check the Wegovy semaglutide tablets page for the latest availability at Pharmica.
Looking for a GLP-1 treatment? Wegovy injectable pens and Mounjaro are both licensed and available at Pharmica.
For a full comparison of Wegovy tablets and the injection, see our Wegovy tablets vs injection guide.
Which weight loss tablet is right for you?
The right choice depends on your circumstances, including your BMI, health history, eating habits and preferences.
Orlistat is a well-established, MHRA-licensed option. It works best if your diet is higher in fat and you're prepared to make the changes needed to manage its side effects.
Wegovy semaglutide tablets are a newer GLP-1 option with strong phase 3 trial data, including greater average weight loss than orlistat in clinical trials. Because they act on your appetite rather than fat absorption, they suit a wider range of eating patterns.
A prescribing clinician can help you check your eligibility, discuss which option fits your health and guide you on the best way forward. You can start a clinical consultation at Pharmica to explore the weight loss treatments available to you.
When to seek further advice
Speak to your GP or prescribing clinician if you:
- Are pregnant, breastfeeding, or planning to conceive, as weight loss medication is generally not appropriate during pregnancy
- Are taking other prescription medications, particularly immunosuppressants such as ciclosporin, as Orlistat can interact with these
- Experience severe or persistent nausea, vomiting, or abdominal pain while taking either treatment
- Have not lost at least 5% of your starting body weight after 12 weeks on Orlistat, as continued use is unlikely to be beneficial
- Have questions about whether a weight loss treatment is appropriate given your personal medical history
Frequently asked questions
Can you take Wegovy semaglutide tablets and Orlistat at the same time?
No. There's no clinical evidence supporting the combined use of oral semaglutide and Orlistat, and taking both isn't recommended. They work through entirely different mechanisms, and combining weight loss treatments without medical supervision carries a risk of increased side effects and unknown interactions. A prescribing clinician can advise on the most appropriate single treatment for your circumstances.
Is oral semaglutide stronger than Orlistat?
In clinical trials, oral semaglutide produced greater average weight loss than Orlistat, approximately 16.6% of body weight over 64 weeks compared to around 10.2% over 12 months with Orlistat. However, individual results vary depending on diet, lifestyle, and treatment adherence, and the two trials weren't designed to be directly compared. "Stronger" also depends on what you're measuring. Orlistat is well-tolerated by many people and has a strong long-term safety record built over decades of use in the UK.
Will Wegovy semaglutide tablets be available on the NHS?
Wegovy semaglutide tablets aren't currently licensed in the UK, so there's no NHS pathway for them yet. Whether they'll be made available on the NHS after MHRA approval will depend on NICE guidance and NHS England commissioning decisions. For context, injectable Wegovy is available through some NHS specialist weight management services but access remains limited. Orlistat is currently the oral weight loss treatment most commonly prescribed on the NHS.
What happens if you eat a high-fat meal while taking Orlistat?
The gastrointestinal side effects of Orlistat - oily stools, increased bowel urgency, flatulence - are directly triggered by fat in the diet. Eating a meal high in fat while taking Orlistat means more undigested fat passes through the gut, which significantly increases the likelihood and severity of these effects. Keeping dietary fat to around 30% of calories or less per meal is the most effective way to avoid them.
Can you switch from Orlistat to Wegovy Semaglutide Tablets?
Yes. Now that Wegovy semaglutide tablets are MHRA-approved (11 June 2026) and expected to be available by private prescription within weeks, switching is a matter of stopping Orlistat and starting the new treatment under clinical supervision once it's available. There's no known wash-out period required between the two, as they work through entirely different mechanisms. A prescribing clinician would need to assess your suitability and initiate the dose escalation schedule for oral semaglutide.
Do Wegovy semaglutide tablets work without dieting?
Clinical trials of oral semaglutide were conducted alongside a reduced-calorie diet and lifestyle support, so the trial results reflect combined use. Semaglutide does reduce appetite, which often naturally leads to lower calorie intake, but the best outcomes in trials came from pairing the medication with conscious dietary changes. It's not recommended to rely on the medication alone without any attention to diet and activity.
Does Orlistat affect medications?
Orlistat can affect the absorption of certain medications, most notably ciclosporin (an immunosuppressant), levothyroxine (thyroid medication), and anticoagulants such as warfarin. It can also reduce the absorption of fat-soluble vitamins, which is why a daily multivitamin is recommended. Always inform your prescribing clinician of any other medications you're taking before starting Orlistat.
References
- Wharton S, et al. Oral semaglutide at a dose of 25 mg in adults with overweight or obesity (OASIS 4). New England Journal of Medicine. 2025;393(11):1077-1087. doi:10.1056/NEJMoa2500969
- Torgerson JS, et al. XENical in the Prevention of Diabetes in Obese Subjects (XENDOS) Study. Diabetes Care. 2004;27(1):155-161. doi:10.2337/diacare.27.1.155
- Roche Products Limited. Xenical (orlistat) 120mg Summary of Product Characteristics. Electronic Medicines Compendium (eMC). medicines.org.uk
This article is intended for informational purposes only and does not replace professional medical advice. Always read the patient information leaflet supplied with your medication and speak to a healthcare professional if you have specific concerns.