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, lead 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, a medicine that acts on two hormone receptors in your body: GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide).
Both are incretins, gut hormones your body releases naturally after eating. They tell your brain you're 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 activates both receptors at once, which is thought to be part of why it has such a strong effect on appetite. Most people find it much easier to eat less, without the constant hunger that makes dieting hard to keep up.
Some people also notice less "food noise", the constant thoughts about eating that can undo even the best dietary intentions.
Mounjaro is a once-weekly injection under the skin, using a pre-filled pen. You start on 2.5mg a week, and the dose goes up every four weeks to a maximum of 15mg, depending on how well you tolerate it and how you respond.
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 fatty acids your body can absorb. Orlistat stops them working.
That means around a third of the fat you eat isn't absorbed. That undigested fat passes through your gut and out in your stools.
Orlistat comes as a capsule, usually taken three times a day with meals that contain fat. 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 assessment.
Because orlistat doesn't affect your appetite, cutting back on what you eat is down to you. It works best when you keep fat to a moderate level, roughly 30% of your daily calories.
Do not eat high-fat meals while taking orlistat. They make side effects like oily stools and urgency much more likely.
How do Mounjaro and orlistat compare on effectiveness?
Clinical trial data shows a big difference in how much weight people lose with each treatment.
In the SURMOUNT-1 phase 3 trial, a large study of tirzepatide for weight management in adults without diabetes, people lost an average of 16.0%, 21.4% and 22.5% of their body weight over 72 weeks at the 5mg, 10mg and 15mg doses. That compares with 2.4% on placebo.1 These are among the largest weight loss results seen in phase 3 trials of licensed weight management medicines.
Orlistat leads to more modest results. One meta-analysis found that orlistat led to around 2.4kg more weight loss than in control groups. That's statistically significant, but fairly small.2
The gap reflects how differently each medicine works. Mounjaro reduces your appetite, which makes it easier to keep up a significant calorie deficit. Orlistat only cuts the calories you absorb from fat, and does nothing for your appetite, so sticking to a calorie-controlled diet is entirely down to you.
Keep a simple monthly note of your weight and waist size. It makes progress reviews with your prescriber much easier.
Neither treatment replaces diet and lifestyle changes. Both are licensed for use alongside a reduced-calorie diet and more physical activity, and with both, weight can come back once you stop if those changes aren't in place.
Side effects: what to expect from each treatment
Mounjaro side effects
The most common side effects of Mounjaro are digestive. They're most noticeable in the early weeks of treatment or after a dose increase.
According to Mounjaro's prescribing information, nausea, diarrhoea, vomiting and constipation are "very common", meaning they affect more than 1 in 10 people.3 These tend to ease as your body adjusts.
More serious but less common risks include acute pancreatitis and gallbladder problems, including gallstones, which can happen more often during rapid weight loss. Severe dehydration can also lead to acute kidney injury. All of these need prompt medical assessment if symptoms develop.
Severe upper tummy pain that spreads to your back? Get urgent medical help, as it can be a sign of pancreatitis.
Mounjaro slows how quickly food leaves your stomach, which can reduce how well some oral medicines are absorbed, including the combined contraceptive pill.
If you take oral contraception, use a barrier method such as condoms as well for four weeks after starting tirzepatide, and for four weeks after each dose increase.3
A full overview is in our Mounjaro side effects guide.
Orlistat side effects
Orlistat's side effects are almost all digestive, and they're directly linked to how much unabsorbed fat is 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.4 These are more likely after high-fat meals.
They tend to ease over time, especially as you get more consistent about cutting back on fat. But for some people, they stay bothersome enough to affect their daily life or make it hard to stick with treatment.
Orlistat also reduces how well you absorb the fat-soluble vitamins A, D, E and K. A daily multivitamin is recommended during treatment to keep your vitamin levels up. Take it at bedtime, or at least two hours after your orlistat dose.4
Orlistat can interact with some medicines, including warfarin, ciclosporin and amiodarone. 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.3 That's the basis private prescribers use.
For NHS prescribing, NICE technology appraisal TA1026 (published December 2024) sets a stricter threshold. It recommends tirzepatide for adults with a BMI of at least 35 and at least one weight-related health condition.5
A lower BMI threshold (2.5 lower) applies to people from South Asian, Chinese, other Asian, Middle Eastern, Black African or African-Caribbean backgrounds.
NHS England is rolling it out in phases, starting with those in greatest need. That initially means people with a BMI of 40 or above and at least four qualifying health conditions, with eligibility expected to widen over time.5
Mounjaro isn't suitable during pregnancy or breastfeeding. Tell your prescriber if you or a family member has had a rare type of thyroid cancer called medullary thyroid carcinoma, or a genetic condition called multiple endocrine neoplasia type 2 (MEN2), so they can take this into account.
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 at least one weight-related risk factor, like type 2 diabetes, high blood pressure or high cholesterol.4
It's usually started alongside dietary advice. Treatment should be stopped after 12 weeks if you haven't lost at least 5% of your starting weight.4
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 assessment.
Because orlistat's criteria are less strict, and the lower dose is available without a prescription, it's often easier to access if you don't yet meet the BMI or health condition requirements for Mounjaro.
Orlistat isn't recommended during pregnancy or breastfeeding, and should be used with caution if you take ciclosporin, warfarin or amiodarone.
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 - tends to lead to much greater weight loss, and is better suited to people with obesity, especially those 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 access, with no injection needed. It may be a practical starting point if you're overweight rather than obese, prefer a tablet, or don't yet meet the criteria for Mounjaro. How well it works depends heavily on sticking to a low-fat diet.
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 stand-alone fix.
When to seek further advice
Contact your GP or prescribing clinician if you:
- Experience severe or persistent nausea, vomiting, abdominal pain, or diarrhoea on either treatment
- Develop symptoms consistent with pancreatitis while taking Mounjaro: severe upper abdominal pain, particularly radiating to the back
- Notice signs of gallbladder problems: pain in the upper right abdomen, especially after fatty meals
- Are taking oral contraceptives and have recently started Mounjaro or increased your dose
- Are taking warfarin or ciclosporin and are prescribed orlistat
- Have lost less than 5% of your starting body weight after 12 weeks on orlistat, or after six months on Mounjaro at the maximum tolerated dose, as your clinician may need to reassess suitability
Do not stop either treatment without speaking to your prescriber first, as a structured dose review may be appropriate.
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
- Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038
- Bhaskaran 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
- Eli Lilly Nederland B.V. Mounjaro (tirzepatide) Summary of Product Characteristics. Electronic Medicines Compendium (eMC). medicines.org.uk/emc
- Roche Products Ltd. Xenical (orlistat 120mg) Summary of Product Characteristics. Electronic Medicines Compendium (eMC). medicines.org.uk/emc
- National Institute for Health and Care Excellence. Tirzepatide for managing overweight and obesity (TA1026). December 2024. nice.org.uk/guidance/ta1026
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.