Two oral weight loss treatments, two completely different approaches. Orlistat works in the gut, blocking the absorption of dietary fat. Wegovy semaglutide tablets work via the GLP-1 hormone pathway, reducing appetite and slowing gastric emptying. Both are taken as tablets, but that's roughly where the similarities end.
This guide breaks down how each treatment works, what the clinical evidence shows, who each one suits, and what the key practical differences are, so you can make sense of the choice between them.
What Are Wegovy Semaglutide Tablets?
Wegovy semaglutide tablets contain semaglutide, a GLP-1 receptor agonist. GLP-1 (glucagon-like peptide-1) is a hormone the body naturally produces after eating. It signals to the brain that you have eaten, reduces appetite, and slows the rate at which food leaves the stomach.
By mimicking this hormone, oral semaglutide reduces hunger and food cravings, helping you feel fuller on smaller portions. This makes it easier to maintain a calorie deficit over time without the persistent hunger that often undermines dieting.
Semaglutide has been widely used in injectable form for several years. The oral tablet formulation, branded as Wegovy semaglutide tablets, was approved by the US Food and Drug Administration (FDA) in December 2025 following the Phase 3 OASIS 4 clinical trial. As of June 2026, the treatment is under review by the UK's Medicines and Healthcare products Regulatory Agency (MHRA), with a decision expected later in 2026. It's not yet licensed for use in the UK as a weight loss treatment.
What Is Orlistat?
Orlistat is a lipase inhibitor. Rather than acting on the brain or appetite, it works locally in the gut by attaching to the lipase enzymes responsible for breaking down dietary fat. By preventing roughly one third of the fat you eat from being absorbed, it reduces the overall calorie contribution 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 dose of 60mg is also available without a prescription under the brand names Orlos and Alli. Unlike Wegovy semaglutide tablets, Orlistat is available to buy now through regulated online pharmacies and GP practices.
How Do They Work Differently?
The core distinction is where each treatment acts in the body. Orlistat acts in the gut, physically blocking fat absorption. Wegovy semaglutide tablets act on the brain and gastrointestinal system via the GLP-1 pathway, reducing appetite and slowing gastric emptying.
This means they address weight gain from different angles. Orlistat relies on reducing the calories absorbed from dietary fat, making it most effective when combined with a low-fat diet. Wegovy semaglutide tablets work by reducing appetite and food intake overall, which means they can be effective across a broader range of dietary patterns.
Because they work differently, they also have distinct side effect profiles and suitability criteria, which are worth understanding before choosing a treatment.
How Effective Is Each Treatment?
Clinical trials provide the clearest comparison of what each treatment can achieve.
In the OASIS 4 Phase 3 trial, adults taking oral semaglutide 25mg once daily alongside a reduced-calorie diet and lifestyle support lost an average of 16.6% of their body weight over 64 weeks, with full treatment adherence. Around one in three participants achieved 20% or more weight loss during the trial.1 On an intention-to-treat basis, accounting for participants who discontinued, average weight loss was approximately 13.6%.
For Orlistat, clinical trial data show that individuals who took Orlistat 120mg alongside a calorie-restricted diet lost an average of 10.2% of their body weight over one year, compared to 6.1% in those who dieted without medication.2 Around 67% of people taking Orlistat lost at least 5% of their body weight within 12 weeks, with continued losses for many over the following months.
Both treatments produce clinically meaningful weight loss when used consistently and alongside healthy lifestyle changes. Oral semaglutide has demonstrated greater average reductions in body weight in clinical trials, though head-to-head comparisons between the two are limited.
Who Is Each Treatment Suitable For?
Wegovy Semaglutide Tablets
Based on the criteria used in the OASIS 4 trial and US licensing data, Wegovy semaglutide tablets are intended for 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.1 UK eligibility criteria will be confirmed following MHRA approval and subsequent NICE guidance.
Wegovy Semaglutide Tablets may be particularly suitable for people who prefer oral medication over injections, have not achieved sufficient results 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. Those with a BMI of 28 or above may also be eligible if they have associated risk factors such as type 2 diabetes, high blood pressure, or high cholesterol.3 Orlistat is available now and can be accessed through a clinical consultation at Pharmica without a GP visit.
Orlistat tends to suit people who eat a diet with a relatively high fat content and want to reduce fat absorption directly, or those who prefer a treatment that has a long track record of use in the UK.
What Are the Side Effects?
Both treatments can cause gastrointestinal side effects, though the nature of these differs between the two.
Wegovy Semaglutide Tablets
The most common side effects of oral semaglutide are nausea, vomiting, diarrhoea, constipation, and stomach discomfort. These tend to be most pronounced during the dose escalation phase, as the body adjusts to the medication, and typically improve over time. Starting at a lower dose and increasing gradually helps reduce the likelihood and severity of these effects.
Orlistat
Orlistat's side effects are directly related to its mechanism of action. Because it prevents fat from being absorbed, undigested fat passes through the gut and can cause oily stools, increased bowel frequency, flatulence, and in some cases faecal urgency or leakage. These effects are more pronounced when meals are high in fat. Keeping fat intake below 30% of total calories per meal significantly reduces the risk of these side effects.
Orlistat can also reduce the absorption of fat-soluble vitamins A, D, E, and K. For this reason, a daily multivitamin such as OneVit Complete Multivitamin is recommended alongside Orlistat treatment, taken at least two hours before or after the capsule.4
How Do You Take Each Treatment?
Orlistat 120mg is taken three times daily, with each main meal. It should be swallowed whole before, during, or up to one hour after eating. If a meal's missed or contains no fat, the dose can be skipped.
Wegovy semaglutide tablets are taken once daily in the morning, on an empty stomach, with no more than a small sip of water. Nothing other than water should be consumed for at least 30 minutes after taking the tablet, to allow the medication to be absorbed properly. This is because oral semaglutide uses a delivery mechanism called SNAC technology to improve absorption through the stomach lining, which is sensitive to food and other liquids.
Treatment with Wegovy semaglutide tablets follows a dose escalation schedule, starting at a lower strength and increasing gradually towards the 25mg maintenance dose.
What Is the Difference in Availability?
This is currently a meaningful practical distinction. Orlistat is available to buy now in the UK through Pharmica, following a short clinical consultation. Wegovy semaglutide tablets are not yet available in the UK. They're under review by the MHRA, with a decision expected later in 2026. You can register your interest on the Wegovy semaglutide tablets product page to be notified when they become available at Pharmica.
If you're looking for a GLP-1-based treatment that's available now, Wegovy injectable pens and Mounjaro are both currently licensed and in stock at Pharmica.
Which Weight Loss Tablet Is Right for You?
The right choice depends on your individual circumstances, including your BMI, health history, dietary habits, and personal preferences.
Orlistat is a well-established, MHRA-licensed option available right now. It's most effective for people who eat a higher-fat diet and are prepared to make the dietary adjustments needed to manage its side effects. It suits those who want a tablet-based treatment without a waiting period for regulatory approval.
Wegovy semaglutide tablets represent a newer GLP-1 approach with strong Phase 3 trial data, including greater average weight loss than Orlistat in clinical trials. They act on appetite rather than fat absorption, making them suited to a broader range of dietary patterns. However, they're not yet licensed in the UK, and a confirmed availability date remains subject to MHRA review.
A prescribing clinician can help you assess your eligibility, discuss which option aligns with your health profile, and guide you on the best route forward. You can start a clinical consultation at Pharmica today to explore the weight loss treatments currently 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?
In principle, yes - once Wegovy semaglutide tablets are licensed in the UK and you meet the eligibility criteria, switching would be a matter of stopping Orlistat and starting the new treatment under clinical supervision. 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. Once-daily oral semaglutide 25 mg in adults with obesity or overweight (OASIS 4): a phase 3b, randomised, double-blind, placebo-controlled trial. New England Journal of Medicine. 2025. FDA approval announcement: Novo Nordisk, 22 December 2025. novonordisk.com
- 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
- NHS. Orlistat. NHS.uk. nhs.uk/medicines/orlistat
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.