Last reviewed: 21 March 2026
What Is Semaglutide?
Semaglutide is a GLP-1 receptor agonist medication originally developed to treat type 2 diabetes. It was later approved for chronic weight management under the brand name Wegovy. Semaglutide works by mimicking the hormone GLP-1, which is naturally released after eating. It signals the brain to feel full, slows gastric emptying, and reduces appetite, leading to significant and sustained weight loss.
In clinical trials, semaglutide (2.4mg weekly injection) resulted in an average weight loss of around 15% of body weight over 68 weeks. It is available in the UK via prescription from regulated online pharmacies and clinics following a medical consultation.
What Is Orlistat?
Orlistat is an oral weight loss medication that works by inhibiting pancreatic lipase, an enzyme responsible for breaking down dietary fat. By blocking approximately one-third of the fat consumed in a meal, orlistat reduces calorie absorption. The undigested fat passes through the digestive system and is excreted.
Orlistat is available as a prescription medication (Xenical, 120mg) and as an over-the-counter option (Alli, 60mg) in the UK. It is one of the longest-established weight loss medications and is recommended by the NHS for eligible patients.
Key Differences
Understanding the differences between semaglutide and orlistat is essential for making an informed choice:
Mechanism of Action
Semaglutide acts on the brain’s appetite regulation centres to reduce hunger and caloric intake, while orlistat works locally in the gut to prevent fat absorption. They target entirely different physiological pathways.
Effectiveness
Semaglutide consistently outperforms orlistat in clinical trials. Semaglutide users lose on average 12–15% of body weight, while orlistat users typically lose 5–8%. Semaglutide is considered the more powerful treatment for significant weight management.
Side Effects
Semaglutide’s most common side effects include nausea, vomiting, diarrhoea, and constipation, particularly during dose escalation. Orlistat’s side effects are primarily gastrointestinal, including oily stools, frequent bowel movements, and flatulence, especially after consuming high-fat meals.
Cost
Semaglutide (Wegovy) is significantly more expensive than orlistat, with monthly costs typically ranging from £150–£300+ in UK private clinics and online pharmacies. Orlistat is considerably more affordable, particularly the OTC Alli version, and is available on NHS prescription for qualifying patients.
Availability
Orlistat has been available in the UK for over two decades and is widely stocked by NHS pharmacies and online providers. Semaglutide injections (Wegovy) have faced supply constraints in the UK following high global demand, though availability is improving. Both require a medical consultation for prescription versions.
Which Should You Choose?
Choosing between semaglutide and orlistat depends on your health profile, weight loss goals, budget, and personal preferences. Consider the following:
- Choose semaglutide if you have significant weight to lose, have not responded well to orlistat, or are prepared for a weekly injection and can afford the higher cost.
- Choose orlistat if you prefer an oral medication, are on a tighter budget, or are eligible for NHS prescription support. It works best when combined with a lower-fat diet.
Always consult your GP or an online prescriber before starting any weight loss medication. For broader guidance on managing your weight, visit NHS Healthy Weight.
You may also find our article on best UK online pharmacies for weight loss treatments helpful when deciding where to obtain your prescription.
FAQ
Is semaglutide better than orlistat for weight loss?
Clinical evidence shows semaglutide produces significantly greater weight loss than orlistat. However, semaglutide is more expensive and requires weekly injections, while orlistat is an affordable oral option suitable for long-term use.
Can I get semaglutide or orlistat on the NHS?
Orlistat is available on NHS prescription for patients with a BMI of 28 or above with weight-related conditions, or BMI of 30 and above. Semaglutide (Wegovy) is available through NHS specialist weight management services for eligible patients, though access remains limited. Both are available via private prescription from regulated UK online pharmacies.
How long do I need to take semaglutide or orlistat?
Both medications are typically used as long-term treatments. Weight may return if medication is stopped without maintaining lifestyle changes. Your prescriber will advise on the appropriate duration based on your health goals and response to treatment.