Mounjaro vs Orlistat: key differences explained

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Ana Carolina Goncalves

Medically Reviewed By:

Ana Carolina Goncalves

GPhC Number 2088658

Rehma Gill

Written By:

Rehma Gill

GPhC Number 2225869

Updated: 25 August 2026

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Two of the most prescribed weight loss treatments in the UK work in completely different ways, and choosing between them isn't as straightforward as it might look.

Been looking into weight loss treatments? You've probably come across both Mounjaro and orlistat. They're both available in the UK and both used to support weight management, but that's roughly where the similarities end.

These two medicines work in completely different ways, led to very different results in clinical trials and suit different people. This guide explains how Mounjaro and orlistat compare, so you can have a more informed conversation with your prescriber about which might be right for you.


How does Mounjaro work?

Mounjaro contains tirzepatide. It acts on two hormone receptors in your body: GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide).

Both are gut hormones your body releases naturally after eating. They help you feel full, slow how quickly food leaves your stomach and help regulate your blood sugar.

Mounjaro works on your appetite. Orlistat works on the fat in your food. That difference shapes almost everything else.

Tirzepatide acts on both receptors at once. Many people find it easier to eat less, because they feel less hungry.

Mounjaro is a once-weekly injection under the skin, using a pre-filled pen. You start on 2.5mg a week. After four weeks, the dose usually goes up to 5mg a week.1

After that, any further increases are made only if you need them. Each step is 2.5mg, after at least four weeks on your current dose, up to a maximum of 15mg.1 Not everyone needs the highest dose, and your prescriber will guide you.


How does orlistat work?

Orlistat works in a completely different way. Rather than affecting your appetite or hormones, it acts locally in your gut.

It blocks the enzymes that break down the fat you eat (gastric and pancreatic lipases). Normally, these turn fat from your food into a form your body can absorb. Orlistat stops them working.

That means around a third of the fat from your food isn't absorbed.2 That undigested fat passes through your gut and out in your stools.

Orlistat comes as a capsule, taken with each main meal that contains fat, usually three times a day.3 The prescription strength, sold as Xenical or generic orlistat 120mg, needs a clinical assessment. A lower 60mg dose, branded as Alli, is available over the counter from pharmacies after a short pharmacist check.

Because orlistat doesn't affect your appetite, cutting back on what you eat is down to you. It's designed to go with a balanced, reduced-calorie diet with about 30% of calories from fat, spread across three main meals.3

Mounjaro vs orlistat at a glance Mounjaro works on your appetite by acting on GLP-1 and GIP; orlistat stops around a third of the fat in your food being absorbed. Mounjaro is a once-weekly injection from 2.5mg up to a maximum of 15mg; orlistat is a capsule taken with each main meal that contains fat, at 120mg on prescription or 60mg over the counter. Mounjaro is licensed from a BMI of 30, or 27 with a weight-related condition; prescription orlistat from a BMI of 30, or 28 with weight-related risk factors. The key differences Mounjaro (tirzepatide) Orlistat Works on Your appetite, via GLP-1 and GIP The fat in your food Taken as Once-weekly injection Capsule with each main meal that contains fat Doses 2.5mg, up to a maximum of 15mg 120mg on prescription, 60mg over the counter Licensed BMI 30, or 27 with a weight-related condition 30, or 28 with weight-related risk factors Source: Mounjaro KwikPen and Xenical 120mg SmPCs (emc).

Do not take orlistat with a very fatty meal. Side effects like oily stools and urgency become much more likely.


How do Mounjaro and orlistat compare on effectiveness?

Clinical trial data shows a big difference in how much weight people lost with each treatment. But the two have never been tested against each other in the same trial, so treat the figures as a general guide.

SURMOUNT-1 was a large trial of tirzepatide for weight management in adults without diabetes. Among people who took it as planned, average weight loss over 72 weeks was 16.0%, 21.4% and 22.5% of body weight at the 5mg, 10mg and 15mg doses, compared with 2.4% on placebo.4

Including everyone who started, even those who stopped early, the figures were 15.0%, 19.5% and 20.9%, compared with 3.1% on placebo.4

Average weight loss in the SURMOUNT-1 trial In the SURMOUNT-1 trial, including everyone who started treatment, average weight loss over 72 weeks was 15.0% on tirzepatide 5mg, 19.5% on 10mg and 20.9% on 15mg, compared with 3.1% on placebo. Average weight loss over 72 weeks, including people who stopped early Tirzepatide 5mg 15.0% Tirzepatide 10mg 19.5% Tirzepatide 15mg 20.9% Placebo 3.1% Source: Jastreboff et al. (2022), SURMOUNT-1 trial, New England Journal of Medicine.

Orlistat's results are more modest. In a review of trials in adults with type 2 diabetes or at high risk of it, people on orlistat lost around 2.4kg more than those in the comparison groups.5

Keep a simple monthly note of your weight and waist size. It makes progress reviews with your prescriber much easier.

The gap partly reflects how differently each medicine works. Mounjaro reduces your appetite, which can make it easier to keep up a calorie deficit. Orlistat only cuts the calories you absorb from fat, so sticking to a calorie-controlled diet is down to you.

Neither treatment replaces diet and lifestyle changes. Both are licensed for use alongside a reduced-calorie diet.1,3 And with either one, weight can come back once you stop if those changes aren't kept up.


Side effects: what to expect from each treatment

Mounjaro side effects

The most common side effects of Mounjaro are digestive. Nausea, diarrhoea and vomiting were more common while the dose was being increased, and became less common over time.1

In the weight management trials, nausea, diarrhoea, vomiting and constipation were very common, meaning they affect more than 1 in 10 people.1 If they don't settle or are severe, speak to your prescriber.

Gallstones are common, and acute pancreatitis is uncommon.1 Sickness and diarrhoea can also lead to dehydration, which can affect your kidneys, so try to keep your fluids up.1

Pancreatitis is uncommon, but it's serious. The warning sign to know is severe tummy pain that won't settle.

If you have persistent, severe tummy pain, stop Mounjaro and get medical help straight away. If pancreatitis is confirmed, it should not be restarted.1

Mounjaro may also make the combined pill and other oral contraceptives less reliable. If you take one, switch to a non-oral method, or use a barrier method such as condoms as well, for four weeks after starting and for four weeks after each dose increase.1

A full overview is in our Mounjaro side effects guide.

Orlistat side effects

Orlistat's side effects are almost all digestive, and they're linked to the unabsorbed fat passing through your gut.

The most commonly reported include oily or fatty stools, oily spotting, needing the toilet more often, wind (sometimes with an oily discharge) and, in some cases, an urgent need to go.3 These are more likely after high-fat meals.

They tend to become less frequent the longer you take it.3 But for some people, they stay bothersome enough to make it hard to stick with treatment.

Orlistat can reduce how well you absorb the fat-soluble vitamins A, D, E and K. Your prescriber may suggest a daily multivitamin. If so, take it at bedtime, or at least two hours after your orlistat dose.3

Orlistat can interact with some medicines, including warfarin, ciclosporin and amiodarone.3 If you take any of these, tell your prescriber before starting orlistat.

Our orlistat side effects guide has the full details.


Who is eligible for Mounjaro in the UK?

Whether you can get Mounjaro depends on whether you're going through the NHS or privately, and the criteria are quite different.

Mounjaro is licensed in the UK for weight management in adults with a BMI of 30 or above, or from 27 with at least one weight-related health condition. Those include high blood pressure, high cholesterol, obstructive sleep apnoea, heart disease, prediabetes and type 2 diabetes.1 Private prescribers work within this licence, though services can set their own stricter rules. You can check your BMI with our BMI calculator.

For NHS prescribing, NICE technology appraisal TA1026 sets a higher threshold. It recommends tirzepatide for adults with a BMI of at least 35 and at least one weight-related health condition.6 A lower BMI threshold (usually 2.5 lower) applies to people from South Asian, Chinese, other Asian, Middle Eastern, Black African or African-Caribbean backgrounds.6

Meeting the licence isn't the same as qualifying on the NHS. The NHS rules are narrower, for now at least.

The NHS is rolling it out in phases, starting with those in greatest need. Since around June 2026, that means people with at least four qualifying health conditions and a BMI of 35 or above. More people are expected to qualify from around March 2027.6

Mounjaro must not be used during pregnancy. If you're planning a pregnancy, stop it at least one month beforehand.1 If you're breastfeeding, get individual advice from your prescriber. The product information says it could be considered, but NHS advice is more cautious and says it isn't used while breastfeeding.1,7


Who is eligible for orlistat in the UK?

Orlistat 120mg (prescription strength) is licensed for adults with a BMI of 30 or above, or from 28 with weight-related risk factors.3

It's started alongside a reduced-calorie diet. Treatment should be stopped after 12 weeks if you haven't lost at least 5% of your starting weight.3

Alli 60mg is available over the counter from pharmacies, without a prescription, for adults aged 18 or over with a BMI of 28 or above, after a short pharmacist check. See how the two strengths compare in our Xenical vs Alli guide.

So the licensed BMI thresholds aren't simply lower for orlistat. For people who are overweight rather than obese, orlistat's 28 is actually slightly higher than Mounjaro's 27. But orlistat is widely prescribed and the lower dose is available without a prescription, so in practice it's often easier to get.

Orlistat must not be used while breastfeeding, and caution is needed in pregnancy.3 It's also used with caution if you take ciclosporin, warfarin or amiodarone.3


Which treatment is right for you?

There's no single answer, and the decision should always be made with a prescriber, based on your health. That said, a few general principles apply:

  • Mounjaro - led to much greater average weight loss in trials than orlistat did in separate trials. It may suit people with a higher BMI or weight-related conditions who are likely to benefit from a bigger reduction. The once-weekly injection suits people who find daily tablets hard to keep up with.
  • Orlistat - usually easier to get, with no injection needed. It may be a practical option if you prefer a capsule or don't meet the criteria for Mounjaro. How well it works depends heavily on sticking to a lower-fat diet.

Want to see Wegovy in the mix too? Our Wegovy vs Mounjaro vs orlistat comparison covers all three.

The best results with either treatment come from using medication as one part of a wider approach to diet, activity and habits, not as a standalone fix.

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When to seek further advice

Contact your GP or prescribing clinician if you:

  • Have severe or persistent nausea, vomiting, tummy pain or diarrhoea on either treatment
  • Notice signs of gallbladder problems, such as pain in the upper right of your tummy
  • Take oral contraceptives and have recently started Mounjaro or increased your dose
  • Take the contraceptive pill and have severe diarrhoea while on orlistat, as the pill may not be absorbed properly
  • Take warfarin or ciclosporin and are prescribed orlistat
  • Have lost less than 5% of your starting weight after 12 weeks on orlistat, or after six months on the highest dose of Mounjaro you can manage, as your clinician may need to review your treatment

Severe, persistent tummy pain is different. Stop Mounjaro and get urgent medical help, as it can be a sign of pancreatitis.1

For any other change, like stopping, switching or changing your dose, agree a plan with your prescriber first.


Frequently asked questions

Is Mounjaro better than orlistat for weight loss?

Clinical trial data shows Mounjaro produces significantly greater weight loss than orlistat. In the SURMOUNT-1 trial, tirzepatide produced average weight reductions of up to 22.5% over 72 weeks, compared to the modest additional weight loss of around 2.4 kg beyond diet and exercise seen with orlistat in clinical studies. However, "better" depends on your individual circumstances. Mounjaro has stricter eligibility criteria, requires a weekly injection, and costs more. Orlistat is more accessible and available without a prescription at the lower dose, making it a practical option for people who are overweight rather than obese, or who prefer an oral treatment over a weekly injection.

Can I take Mounjaro and orlistat together?

No. There is no clinical evidence supporting the combined use of Mounjaro and orlistat, and taking both simultaneously would not be appropriate. If you are already taking orlistat and want to switch to Mounjaro, speak to your prescriber. They will assess whether you meet the eligibility criteria and guide you through the transition.

Can I get Mounjaro or orlistat on the NHS?

Orlistat 120 mg is available on the NHS for adults with a BMI of 30 or above, or from 28 with a weight-related health condition. Mounjaro is available on the NHS following NICE approval (TA1026, December 2024), but access is currently restricted to those with the highest clinical need: initially adults with a BMI of 40 or above and at least four weight-related comorbidities. Both treatments require a clinical assessment. Mounjaro is also available privately with less restrictive criteria, in line with its officially licensed indications.

What happens when you stop taking Mounjaro or orlistat?

Weight regain is common after stopping either treatment if the underlying diet and lifestyle changes are not maintained. With Mounjaro, the appetite-suppressing effects of tirzepatide cease when the injections stop, and hunger typically returns to baseline levels. Clinical studies have shown significant weight regain following discontinuation without continued lifestyle support. Orlistat's effect also stops immediately on discontinuation, as it has no systemic action. In both cases, speaking to your prescriber before stopping is strongly recommended.

Which has fewer side effects - Mounjaro or orlistat?

Both treatments commonly cause gastrointestinal side effects, but the nature of those effects differs. Mounjaro's side effects - nausea, diarrhoea, vomiting - are systemic, driven by its effect on gut hormones and gastric emptying, and tend to improve over time as the body adjusts. Orlistat's side effects - oily stools, flatulence, faecal urgency - are directly caused by unabsorbed fat passing through the gut, and are more controllable through diet: keeping dietary fat intake low significantly reduces their likelihood. Neither is clearly "better" on side effects. It depends on which profile a patient finds more manageable.


References

  1. Eli Lilly and Company Limited. Mounjaro KwikPen solution for injection in pre-filled pen: Summary of Product Characteristics. Electronic Medicines Compendium; 2026. medicines.org.uk/emc
  2. NHS. Orlistat: a medicine to treat obesity. NHS website; 2026. nhs.uk
  3. Neon Healthcare Ltd. Xenical 120 mg hard capsules: Summary of Product Characteristics. Electronic Medicines Compendium; 2023. medicines.org.uk/emc
  4. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038
  5. Ghosal S, Heron N, Mason K, et al. Efficacy of orlistat in type 2 diabetes: a systematic review and meta-analysis. BJGP Open. 2025. doi:10.3399/BJGPO.2025.0058
  6. National Institute for Health and Care Excellence. Tirzepatide for managing overweight and obesity. TA1026. NICE; 2024. nice.org.uk
  7. NHS. Tirzepatide: a medicine to manage type 2 diabetes and treat obesity. NHS website; 2026. nhs.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.

GPhC Number 2225869

Rehma Gill
Authored by:Rehma GillPharmacy
Manager

GPhC Number 2088658

Ana Carolina Goncalves
Reviewed by:Ana Carolina GoncalvesSuperintendent
Pharmacist

Find out more about our team of medical content authors and how we ensure the accuracy of our content with our content guidelines.

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