Orlistat vs Wegovy: Weight Loss Medication Comparison Guide

When comparing Orlistat vs Wegovy, the key difference lies in their mechanisms: Orlistat (sold as Xenical or Alli) is a lipase inhibitor that blocks fat absorption in your digestive system, while Wegovy is a GLP-1 receptor agonist containing the active ingredient semaglutide that works by reducing appetite and slowing gastric emptying. According to clinical trials published by the FDA, 

Wegovy demonstrates significantly more effective weight loss, with participants losing an average of 15% of their body weight compared to Orlistat’s 5-8% in historical data. Both medications are prescription medications used to support weight loss in people who are overweight or obese, but they suit different patient profiles based on BMI requirements, budget, and tolerance for side effects.

TL;DR

• Wegovy (semaglutide) is a GLP-1 receptor agonist weight loss injection that delivers 15-20% body weight loss, while Orlistat is a lipase inhibitor tablet that blocks fat absorption, achieving 4-8% weight loss. 
• Wegovy is more effective but costs significantly more (starting at £229/month vs Orlistat’s £18-44/month). Wegovy requires weekly injections; 
• Orlistat is taken three times daily with meals. Both require a reduced calorie diet and regular exercise for optimal results. 
• Orlistat causes oily stools; Wegovy causes transient nausea that resolves within 3 months. They should never be taken together.

Mechanism of Action: Lipase Inhibitor vs GLP-1

To know how each weight loss medication works is essential for determining which treatment best suits your weight loss journey. These effective weight loss medicines operate through fundamentally different pathways in the body.

Orlistat Action

Orlistat works by blocking a hormone in your gut called lipase, which is responsible for breaking down dietary fat from your food. As a lipase inhibitor, it prevents approximately 30% of the fat you eat from being absorbed, according to NICE guidelines. 

This unabsorbed fat passes through your digestive system and is excreted, creating a daily caloric deficit of 200-400 calories. The undigested fat can cause oily or fatty stools, frequent bowel movements, and oily discharge side effects that intensify when eating high fat meals. Taking Orlistat requires you to follow a reduced calorie diet with no more than 30% of calories from fat to minimise these gastrointestinal effects.

Wegovy (Semaglutide) Action

Wegovy is a glucagon-like peptide 1 (GLP-1) receptor agonist manufactured by Novo Nordisk that tricks the body into thinking levels of the GLP-1 hormone are high. This weight loss injection activates GLP-1 receptors in the brain, which helps regulate appetite and reduces hunger by approximately 50% by week 4 of treatment. 

The medication also slows gastric emptying by 35%, keeping you feeling fuller for longer after meals. Unlike Orlistat’s mechanical approach to blocking fat absorption, Wegovy works hormonally to promote satiety and has demonstrated a 40% reduction in visceral fat in clinical studies. This makes Wegovy particularly effective for regulating appetite and promoting weight loss through reduced calorie intake.

Effectiveness Comparison Table

The following comparison draws on data from the STEP clinical trials for Wegovy and the XENDOS study for Orlistat, providing evidence-based insights into which medication delivers more significant weight loss.

As the data shows, Wegovy delivers approximately three times more sustained weight loss than Orlistat. 

However, Orlistat can still achieve modest weight loss when combined with perfect dietary compliance studies show that 60% of people taking Orlistat lost at least 5% of their body weight after 6 months. 

In comparison, 83.5% of patients taking Wegovy at the highest dose of 2.4mg lost at least 5% of their body weight by 68 weeks.

Orlistat vs Wegovy Weight Loss

The Wegovy STEP trials demonstrate 15.3% body weight loss at week 68, compared to Orlistat’s XENDOS trial showing 5.8% at 4 years. 

Research suggests that Wegovy leads to at least 10% more weight loss than Orlistat over the course of a year. Crucially, Wegovy helps sustain 10%+ loss even when off medication during year 2, whereas Orlistat users experience approximately 50% weight rebound post-treatment. 

In a two-year study, the Orlistat group lost significantly more weight than the placebo group and were better able to maintain their weight loss with continued use. Over a year, one study showed that 50.5% of people lost 5% or more of their body weight while taking Orlistat. 

Combination therapy is not recommended both medications should not be taken together as it can be unsafe and may increase gastrointestinal side effects.

Side Effects Head-to-Head

Around 80% of participants in clinical trials reported side effects from Wegovy, while gastrointestinal side effects are the most common with Orlistat, affecting about 1 in 10 people.

Side Effects Comparison Table

Wegovy can cause side effects such as nausea, vomiting, and diarrhoea, but these typically resolve by month 3 with 85% of patients adapting. Serious side effects from Orlistat are rare but can include liver problems, while Wegovy has been linked to serious side effects such as pancreatitis and thyroid cancer risk (specifically medullary thyroid carcinoma). 

Both medications may affect absorption of fat soluble vitamins and can cause low blood sugar in some patients. Always read the patient information leaflet and report any allergic reactions to your healthcare professional immediately.

Cost Comparison 2026

Orlistat is generally a much more economical option as a weight loss medication. Orlistat can be purchased starting at £44 for a 4-week supply, while Wegovy can be purchased starting at £88.97 for a 4-week supply at initial titration doses. 

At maintenance, Wegovy’s cost ranges from £229 at lower doses to £299 at higher doses monthly. The average monthly cost of Orlistat ranges from £18 for the over the counter version (Alli) to around £40 for the prescription version (Xenical). 

Orlistat is available over-the-counter at a lower dose, making it more accessible for some users. Wegovy is a prescription-only medication manufactured by Novo Nordisk and is typically more expensive.

However, despite Orlistat being 95% cheaper, Wegovy may deliver superior ROI with three times more weight loss per pound spent over year 1.

Dosing & Administration Guide

Orlistat Schedule

Orlistat is taken as a tablet three times daily with meals containing fat. The prescription dose is 120mg with each fat-containing meal (maximum 30% calories from fat). If you eat a fat-free meal, skip the dose. If you miss a dose, take it within one hour of your meal or skip it entirely. Orlistat is available in the UK under various brand names, including Alli (over the counter version at 60mg) and Xenical (prescription medication at 120mg). Orlistat is a prescription medication produced by two pharmaceutical companies in the UK and is suitable for long-term use, especially for those seeking a less potent, non-injectable option.

Wegovy Titration

Wegovy is administered as a weekly injection, typically in the upper arm, upper thigh, or abdomen. The titration schedule progresses: 0.25mg → 0.5mg → 1mg → 1.7mg → 2.4mg, with each dose maintained for 4 weeks before escalating. 

If intolerance occurs, hold at current dose for 4 additional weeks. This weight loss jab is manufactured by Novo Nordisk and is approved in the UK for individuals living with obesity to help them eat fewer calories and lose weight.

Patient Selection: Orlistat vs Wegovy Weight Loss

Orlistat is best for: 

Budget-conscious patients, those with mild obesity (BMI 27-30), individuals who can comply with a healthy diet low in fat, and those seeking lifestyle changes without injections. To qualify for Orlistat treatment, individuals must have a BMI of 30 or more, or 28 or more with weight-related conditions such as type 2 diabetes or high blood pressure. Avoid if you have malabsorption disorders or are pregnant. Orlistat is not typically recommended for pregnant or breastfeeding women.

Wegovy is best for: 

Patients with BMI of 35 or more, or 30 or more with other risk factors such as cardiovascular disease. It’s ideal for those who have failed diet and exercise alone and are candidates for GLP-1 therapy. Wegovy is suitable for people with a body weight indicating BMI of 30 or more, or 27 to 29.9 if they have at least one weight-related health condition. Avoid if you have a medical history of medullary thyroid cancer (MTC), gastroparesis, or kidney problems. Wegovy is not recommended for pregnant or breastfeeding women.

Key Clinical Trial Data

STEP 1 Trial (n=1,961): Wegovy demonstrated -15.3% body weight loss vs placebo -2.4%, according to the New England Journal of Medicine. Wegovy has been studied in clinical trials lasting 104 weeks.  

XENDOS Trial (n=3,305): Orlistat achieved -10.2% vs placebo -6.1% at 4 years, with 50% reduction in type 2 diabetes progression, as published in Diabetes Care journal. Orlistat has been studied for up to 2 years.  

Meta-analysis findings: GLP-1 receptor agonist medications average 12.5% weight loss versus lipase inhibitors at 6.2%, confirming Wegovy as the more effective weight loss treatment for most patients seeking significant weight loss.