Is orlistat the same as Wegovy? No, orlistat and Wegovy are entirely different weight loss medications with distinct mechanisms of action. Orlistat (Xenical, Alli) is a lipase inhibitor taken orally three times daily that blocks approximately 30% of dietary fat absorption in the gut. Wegovy (semaglutide 2.4 mg) is a GLP-1 receptor agonist administered as a once-weekly injection that works systemically to reduce appetite and slow gastric emptying. Whilst both are licensed for weight management in the UK, they differ significantly in how they work, administration routes, side effect profiles, clinical effectiveness, and NHS accessibility. Understanding these differences is essential for making informed treatment decisions.
Quick Answer: Orlistat and Wegovy are not the same medication—they are two distinct weight loss treatments with different mechanisms, administration methods, and effectiveness profiles.
Orlistat and Wegovy are not the same medication — they are two entirely different weight loss treatments that work through distinct mechanisms in the body. This is a common source of confusion for patients seeking pharmaceutical support for weight management, but understanding the fundamental differences is essential for making informed treatment decisions.
Orlistat (brand names Xenical and Alli) is a lipase inhibitor that has been available in the UK since 1998. It works locally in the digestive system to reduce fat absorption from food. Orlistat is available both on prescription (120 mg) and over-the-counter in lower doses (60 mg as Alli).
Wegovy (semaglutide 2.4 mg) is a newer medication, receiving MHRA marketing authorisation for weight management. It belongs to a class of drugs called GLP-1 receptor agonists, originally developed for type 2 diabetes management. Wegovy is administered as a once-weekly subcutaneous injection and works systemically by affecting appetite regulation centres in the brain.
Whilst both medications are licensed for weight management in adults with obesity or overweight with weight-related comorbidities, they differ significantly in their mechanism of action, administration route, side effect profiles, and clinical effectiveness. According to NICE guidance, both can be considered as part of a comprehensive weight management programme that includes dietary modification and increased physical activity. However, NICE Technology Appraisal 875 restricts NHS use of semaglutide 2.4 mg to specialist weight management services, for people with BMI ≥35 kg/m² with at least one weight-related comorbidity (with specific exceptions for BMI 30-34.9 kg/m²), and for a maximum of 2 years. Lower BMI thresholds (by 2.5 kg/m²) apply for people from some minority ethnic groups. The choice between these medications — or whether either is appropriate — depends on individual patient factors, medical history, and treatment goals.
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Start HereOrlistat functions as a gastrointestinal lipase inhibitor, acting locally with minimal systemic absorption. Its mechanism of action is relatively straightforward: it binds to gastric and pancreatic lipases — enzymes responsible for breaking down dietary fats into absorbable components.
By inhibiting these enzymes, orlistat prevents approximately 30% of dietary fat from being digested and absorbed. The undigested fat passes through the gastrointestinal system and is eliminated in the stool. This reduction in caloric absorption creates an energy deficit that, combined with a reduced-calorie diet, promotes weight loss. Importantly, orlistat only affects fat absorption; it does not influence the absorption of carbohydrates or proteins.
The medication must be taken with meals containing fat — typically one capsule (120 mg for prescription strength) three times daily with main meals, or up to one hour after eating. If a meal contains no fat or is missed, the dose should be omitted. Orlistat's effects are immediate and meal-specific, meaning it only works when taken appropriately with food.
Because orlistat reduces fat absorption, it can also affect the absorption of fat-soluble vitamins (A, D, E, and K). According to the SmPC, patients are advised to take a multivitamin supplement at bedtime — at least two hours after taking orlistat — to ensure adequate vitamin intake. The medication's local action in the gut means it has minimal systemic effects, which contributes to its generally favourable safety profile. However, the mechanism of action directly causes the most common side effects: gastrointestinal symptoms including oily stools, flatulence with discharge, faecal urgency, and increased bowel movements, particularly if patients consume high-fat meals.
Treatment should be reviewed after 12 weeks and discontinued if at least 5% weight loss (or at least 3% in people with type 2 diabetes) has not been achieved. The usual maximum treatment duration is up to 2 years. Orlistat has important drug interactions, including with ciclosporin (avoid or monitor closely if unavoidable), warfarin (monitor INR), levothyroxine (separate by at least 4 hours and monitor TSH), antiepileptics (monitor for changes in seizure frequency), and acarbose (avoid combination). Backup contraception is advised if severe diarrhoea occurs in women taking oral contraceptives. Orlistat should not be used during pregnancy or breastfeeding.
The differences between orlistat and Wegovy extend far beyond their mechanisms of action, encompassing administration, side effects, precautions, and accessibility.
Administration and dosing represent a fundamental distinction. Orlistat is taken orally as a capsule three times daily with meals, requiring consistent adherence throughout the day. Wegovy, conversely, is administered as a once-weekly subcutaneous injection, which many patients find more convenient despite the need for self-injection. Wegovy requires dose titration, starting at 0.25 mg weekly and increasing gradually (0.5 mg, 1.0 mg, 1.7 mg) to the maintenance dose of 2.4 mg as tolerated. The injection is typically given in the abdomen, thigh, or upper arm using a pre-filled pen device.
Mechanism and systemic effects differ substantially. Whilst orlistat works locally in the gut with minimal systemic absorption, Wegovy is absorbed into the bloodstream and acts centrally on the brain's appetite regulation centres, as well as slowing gastric emptying. This means Wegovy has broader physiological effects. The SELECT trial has demonstrated cardiovascular benefits with semaglutide 2.4 mg, though this is not currently part of the UK marketing authorisation.
Side effect profiles are markedly different. Orlistat's side effects are predominantly gastrointestinal — oily spotting, flatulence, faecal urgency, and fatty stools — which are directly related to its mechanism and can be managed by reducing dietary fat intake. Wegovy's side effects are primarily nausea, vomiting, diarrhoea, constipation, and abdominal pain, particularly during dose escalation. The Wegovy SmPC includes precautions regarding pancreatitis, gallbladder disease, risk of dehydration and acute kidney injury, and diabetic retinopathy in people with type 2 diabetes. Animal studies have shown thyroid C-cell tumours, though the human relevance is unknown. Neither medication should be used during pregnancy or breastfeeding.
NHS accessibility varies considerably. Orlistat is available over-the-counter in lower doses (Alli 60 mg) and on prescription (Xenical 120 mg). Wegovy requires a prescription and, under NICE TA875, NHS access is restricted to specialist weight management services for people meeting specific BMI criteria, and for a maximum of 2 years.
Clinical trial data demonstrate that Wegovy produces substantially greater weight loss than orlistat, though both medications are effective when used appropriately as part of a comprehensive weight management programme.
Orlistat clinical evidence: The landmark XENDOS study and multiple meta-analyses show that orlistat, combined with lifestyle modification, produces an average weight loss of approximately 3–5% of initial body weight beyond that achieved with lifestyle changes alone over one year. In practical terms, this translates to an additional 3–4 kg weight loss compared to placebo. Long-term studies demonstrate that orlistat can help maintain weight loss and may reduce the incidence of type 2 diabetes in at-risk individuals. The medication's effectiveness is highly dependent on dietary fat restriction — patients who continue consuming high-fat diets experience both reduced efficacy and increased gastrointestinal side effects.
Wegovy clinical evidence: The STEP (Semaglutide Treatment Effect in People with obesity) clinical trial programme demonstrated substantially greater weight loss with Wegovy. In the pivotal STEP 1 trial, participants achieved an average weight loss of approximately 15% of initial body weight over 68 weeks — significantly more than the 2.4% seen with placebo. Nearly one-third of participants lost 20% or more of their body weight. The STEP 2 trial showed somewhat lower but still significant weight loss in people with type 2 diabetes (average 9.6% with Wegovy vs 3.4% with placebo). The STEP 4 extension data showed that weight regain occurs after discontinuation, highlighting the importance of ongoing treatment for maintenance. The SELECT trial, rather than the STEP programme, demonstrated cardiovascular benefits.
Comparative effectiveness: No large head-to-head trials directly compare orlistat and Wegovy, making direct comparisons challenging. Indirect comparisons from separate trials suggest Wegovy produces greater weight loss than orlistat, but such cross-trial comparisons have significant limitations. The choice between medications must be balanced against differences in side effects, administration requirements, and individual patient factors. NICE guidance acknowledges the efficacy of GLP-1 receptor agonists but notes that orlistat remains a valuable option, particularly for patients who cannot tolerate or access newer medications.
Selecting between orlistat and Wegovy requires careful consideration of multiple factors, and this decision should always be made in consultation with a healthcare professional. Neither medication is suitable for everyone, and both require commitment to lifestyle changes for optimal results.
Orlistat may be more appropriate if you:
Prefer oral medication over injections
Have a modest weight loss goal (5–10% of body weight)
Are willing to follow a reduced-fat diet (ideally less than 30% of calories from fat)
Seek an over-the-counter option (Alli 60 mg) or prescription (Xenical 120 mg)
Have no contraindications such as chronic malabsorption or cholestasis
Are prepared to manage potential gastrointestinal side effects through dietary modification
Wegovy may be more suitable if you:
Require more substantial weight loss (>10% of body weight)
Have type 2 diabetes or other weight-related comorbidities
Prefer once-weekly administration despite injection requirement
Can tolerate gastrointestinal side effects during initial dose escalation
Meet NHS eligibility criteria for specialist weight management services
Can adhere to the dose titration schedule and regular monitoring
Important considerations: According to the SmPC, orlistat is indicated for adults with a BMI of 30 kg/m² or above, or 28 kg/m² or above with weight-related risk factors. For Wegovy, NICE TA875 restricts NHS use to specialist weight management services for people with BMI ≥35 kg/m² with at least one weight-related comorbidity (with specific exceptions for BMI 30-34.9 kg/m²), and for a maximum of 2 years. For people from specified minority ethnic groups, these thresholds are reduced by 2.5 kg/m². Both medications should be used alongside a comprehensive weight management programme including dietary changes, increased physical activity, and behavioural support.
When to contact your healthcare provider: Seek medical advice if you experience severe or persistent side effects, particularly severe abdominal pain (potential pancreatitis or gallstones with Wegovy), jaundice/dark urine/itching (potential liver injury with orlistat), allergic reactions, or persistent vomiting/dehydration. Regular monitoring is essential, and treatment should be discontinued if inadequate weight loss is achieved (for orlistat, review at 12 weeks and stop if <5% weight loss, or <3% in people with type 2 diabetes). For Wegovy, regular reviews are required with defined weight loss milestones per the SmPC and NICE guidance. Before starting either medication, a review of potential drug interactions (particularly for warfarin, ciclosporin, levothyroxine, and antiepileptics with orlistat) is recommended. Neither medication should be used during pregnancy or breastfeeding.
There is no established evidence supporting the combined use of orlistat and Wegovy, and this combination is not recommended in standard clinical practice. Any consideration of combining weight loss medications should only be made under specialist supervision with careful monitoring.
Both medications have established safety profiles when used appropriately, but with different risk considerations. Orlistat works locally in the gut with minimal systemic absorption, whilst Wegovy has broader physiological effects requiring monitoring for pancreatitis, gallbladder disease, and other systemic concerns. Your healthcare provider can assess which is more suitable based on your individual medical history.
Orlistat's fat-blocking effects are immediate with each dose, though meaningful weight loss typically becomes apparent within 2–4 weeks. Wegovy requires gradual dose titration over several months, with significant weight loss generally observed after 3–6 months of treatment at the maintenance dose.
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