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Mounjaro vs Wegovy (tirzepatide vs semaglutide): what the head-to-head trial found on weight loss, side effects and who each is licensed for
Trial and licence data, not a recommendation. Tirzepatide and semaglutide compared from the evidence: the SURMOUNT-5 head-to-head trial (20.2% against 13.7% weight loss at 72 weeks), the separate trials behind each licence, side effects and how many people stopped, how each is taken, what is known about heart outcomes, and how NHS access differs.
Mounjaro and Wegovy are the two weekly injections most widely used for weight management in the UK, and "which is better" is one of the most common questions asked about them. One trial has compared them directly: SURMOUNT-5 randomised people to one or the other and measured the result. This article sets out what that trial found, what the separate trials behind each licence found, how the side effects compare, how each is taken, what is known about longer-term outcomes, and how NHS access differs. It reports trial and licence data. It is not a recommendation of either medicine, and the choice between them, or of neither, belongs with a prescriber who knows the person.
What each medicine is
Semaglutide is a GLP-1 receptor agonist: a modified version of a gut hormone that signals fullness, slows stomach emptying and increases insulin release when blood sugar is high. It is sold as Ozempic for type 2 diabetes and as Wegovy, at a higher dose, for weight management. Tirzepatide acts on the same GLP-1 receptor and also on the receptor for a second gut hormone, GIP, which is why it is described as a dual agonist. It is sold as Mounjaro for both type 2 diabetes and weight management. Both are given once a week with a pre-filled pen, both start at a low dose and step up, and both are prescription-only medicines.
Who each is licensed for in the UK
Both medicines are licensed for weight management in adults with a BMI of 30 or more, or 27 or more with at least one weight-related condition, alongside a reduced-calorie diet and increased physical activity. Beyond that the licences differ. Wegovy is also licensed for adolescents aged 12 and over with obesity and a body weight above 60 kg, carries an indication for reducing the risk of major cardiovascular events in adults with established cardiovascular disease and a BMI of 27 or more, and is licensed for a form of fatty liver disease with scarring (MASH) in adults. Mounjaro is licensed for weight management in adults only and, in the same product, for type 2 diabetes in adults and in children aged 10 and over. Semaglutide for type 2 diabetes is a separate product, Ozempic, at lower doses, and Ozempic is not licensed for weight management. A licence says who a medicine may be prescribed for; it does not say who the NHS will fund, which is a separate decision covered below, and it does not replace the judgement of the prescriber about whether the medicine suits the person in front of them.
The head-to-head trial: SURMOUNT-5
SURMOUNT-5 was an open-label trial in 751 adults with obesity, or overweight with a weight-related condition, and without type 2 diabetes. Participants were randomised to the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) for 72 weeks. The primary result was the average percentage change in body weight: 20.2% lost on tirzepatide against 13.7% on semaglutide. Waist circumference fell further on tirzepatide as well, and more people on tirzepatide reached each of the weight-loss thresholds the trial measured.
Four caveats go with that result. The trial was open-label, so participants and doctors knew which medicine was being taken, which matters less for a number on a scale than for reported symptoms but is still a limitation. It was funded by the maker of tirzepatide. It compared tirzepatide with semaglutide at up to 2.4 mg, not with the 7.2 mg dose licensed since. And an average hides a spread: some people on semaglutide lost more than the tirzepatide average, and some on tirzepatide lost little. The trial says which medicine produced more weight loss across a population; it cannot say which will suit a given person.
The separate trials behind each licence
Before SURMOUNT-5, the comparison had to be made across different trials, which is less reliable because the populations and durations differ. Those trials are still the basis of each licence, so their figures are worth having side by side. Each reported two estimates: one counting everyone randomised regardless of whether they stayed on treatment, and one describing people who stayed on it.
| Tirzepatide 15 mg (SURMOUNT-1) | Semaglutide 2.4 mg (STEP 1) |
|---|
| Participants | 2,539 adults, no diabetes | 1,961 adults, no diabetes |
| Duration | 72 weeks | 68 weeks |
| Average weight loss, everyone randomised | about 20.9% | about 14.9% |
| Average weight loss, on treatment | about 22.5% | about 16.9% |
| Placebo group | about 3.1% | about 2.4% |
| Stopped for adverse events | 6.2% (placebo 2.6%) | 7.0% (placebo 3.1%) |
The cross-trial picture and the head-to-head picture agree: a gap of roughly six percentage points of body weight in favour of tirzepatide 15 mg over semaglutide 2.4 mg. Neither comparison included the 7.2 mg semaglutide dose that the Wegovy licence now allows for adults with obesity. In people with type 2 diabetes, both medicines produce smaller weight losses than in people without it, a pattern seen across the class.
Side effects compared
The two medicines share a side-effect profile dominated by the gut: nausea, diarrhoea, vomiting and constipation, most frequent in the weeks after starting and after each dose increase, and easing as a dose is maintained. In SURMOUNT-5, gastrointestinal events were the most common adverse events in both groups, mostly mild to moderate, and mainly during dose escalation. In the separate trials, the proportion of people who stopped treatment because of adverse events was in the same range for both, around six to seven per cent at the doses tested (tirzepatide 15 mg, semaglutide 2.4 mg) against about three per cent on placebo.
The licences share their main warnings: acute pancreatitis, dehydration from severe vomiting or diarrhoea with a risk to the kidneys, and low blood sugar when combined with insulin or a sulfonylurea. Both also list gallstones as a side effect. There are differences in the detail. The tirzepatide licence says that reduced effectiveness of oral contraceptives cannot be ruled out in women with obesity or overweight, and advises switching to a non-oral method, or adding a barrier method, for four weeks after starting and for four weeks after each dose increase. The Wegovy licence says semaglutide is not expected to reduce the effectiveness of oral contraceptives. The semaglutide licences carry a warning about a very rare cause of sudden vision loss. Each medicine's own leaflet is the authority for that medicine, and our separate articles on Mounjaro side effects and on Ozempic and Wegovy side effects go through each list band by band.
How each is taken
| Mounjaro (tirzepatide) | Wegovy (semaglutide) |
|---|
| Frequency | Once weekly | Once weekly |
| Starting dose | 2.5 mg for four weeks | 0.25 mg for four weeks |
| Dose steps | 2.5 mg increases, at least four weeks apart | 0.5, 1 and 1.7 mg, four weeks each |
| Maintenance doses | 5, 10 or 15 mg | 2.4 mg (adults with obesity may be moved to 7.2 mg if needed, after at least four weeks on 2.4 mg; not for adolescents) |
| Device | Pre-filled pen holding four weekly doses (KwikPen) | Pre-filled pen holding four weekly doses (FlexTouch); 7.2 mg as a single-use pen or three 2.4 mg injections |
These are the schedules in the UK product information, described as licence data. The prescriber decides the dose and the pace. The Wegovy licence says a step can be delayed or the dose lowered if gut side effects are significant; the Mounjaro licence sets a minimum of four weeks between steps, not a fixed timetable. Nothing in this table is a suggestion to follow a schedule without one.
Beyond weight: heart, diabetes and other outcomes
Weight is a measurement; what people and health services care about is what follows from it. Here semaglutide has the longer record. The SELECT trial followed about 17,600 people with overweight or obesity and established cardiovascular disease, but without diabetes, for a mean of over three years, and found that semaglutide 2.4 mg reduced the rate of heart attack, stroke or cardiovascular death by 20% compared with placebo. That result led to a cardiovascular risk-reduction indication being added to the Wegovy licence.
Tirzepatide has outcome data in other settings: a large cardiovascular trial in people with type 2 diabetes compared it with another diabetes medicine, not placebo, and it has placebo-controlled trial results in obstructive sleep apnoea and in heart failure with preserved ejection fraction, which are described in its UK product information. Neither is a separate licensed use in the UK. What it does not yet have is a published placebo-controlled cardiovascular outcomes trial in people with obesity and without diabetes, which is the evidence SELECT provides for semaglutide. More weight loss might be expected to mean more benefit, but that is an inference, and the honest position is that the two have not been compared on hard outcomes.
NHS access in England
NICE has recommended both, on different terms. Semaglutide (Wegovy) is recommended under TA875 for adults with a BMI of at least 35 and a weight-related condition, with some exceptions at lower BMI, and only within specialist weight-management services, for a maximum of two years. Tirzepatide is recommended under TA1026 for adults with a BMI of at least 35 and a weight-related condition, and can be prescribed in primary care, but NHS England is phasing access over a number of years beginning with the people at highest clinical need. Lower BMI thresholds apply for people from some ethnic backgrounds. In practice, the medicine someone can obtain on the NHS depends on their local services and where they sit in the phasing. This article covers NHS access only; private prescribing is outside its scope.
After stopping
In the trials, most of the effect on weight did not last once treatment stopped, although average weight remained somewhat below the starting point a year later. In the withdrawal phase of the SURMOUNT-4 trial, people switched from tirzepatide to placebo regained a substantial part of their lost weight over the following year while those who continued kept losing. In the STEP 1 extension, people who stopped semaglutide regained about two-thirds of their loss within a year. On this point the two are alike, and it is one reason the question "which is better" matters less than whether long-term treatment is wanted at all. Our article on stopping GLP-1 medicines covers both trials.
How to read the comparison
- On average weight loss, tirzepatide produced more than semaglutide in the one direct trial, which used semaglutide at up to 2.4 mg: 20.2% against 13.7% at 72 weeks.
- On side effects, the profiles are the same family with similar discontinuation rates; the licences differ in some specific warnings.
- On heart outcomes in people without diabetes, semaglutide has a large placebo-controlled trial and tirzepatide does not yet have a published equivalent.
- On NHS access, the routes differ: specialist services with a two-year limit for Wegovy, phased primary-care access for tirzepatide.
- On stopping, both show regain.
- Averages describe populations. Which medicine, if any, is appropriate for one person depends on their health, other medicines and response, and is a prescriber's decision.
This article is educational content only and is not medical advice or a recommendation to start, stop, switch or choose any medicine. Mounjaro (tirzepatide) and Wegovy (semaglutide) are prescription-only medicines; the figures are from clinical trials and the UK product information and are not predictions for any individual. Anyone considering treatment or experiencing side effects should speak to their GP, prescriber or pharmacist. Vivera Education sells nothing.
Frequently asked
- What did the head-to-head trial of Mounjaro and Wegovy find on weight loss?
- In the one head-to-head trial, SURMOUNT-5, adults with obesity lost an average of 20.2% of their body weight on tirzepatide and 13.7% on semaglutide over 72 weeks. That is an average across a trial population; individual responses vary widely on both medicines.
- What is the difference between tirzepatide and semaglutide?
- Semaglutide activates one hormone receptor, GLP-1. Tirzepatide activates two, GLP-1 and GIP. Both are once-weekly medicines that reduce appetite and slow stomach emptying. Semaglutide is sold as Wegovy for weight management and Ozempic for type 2 diabetes; tirzepatide is sold as Mounjaro for both.
- Are the side effects of Mounjaro and Wegovy different?
- The side-effect family is the same: nausea, diarrhoea, vomiting and constipation, mostly during dose increases. In SURMOUNT-5 gastrointestinal effects were the most common adverse events in both groups and were mostly mild to moderate. The two licences list some different rarer effects, so each product information leaflet should be read for its own medicine.
- Is Mounjaro safer than Wegovy?
- No trial has shown one to be safer than the other. Both licences carry warnings about pancreatitis, dehydration and low blood sugar with certain diabetes medicines, and both list gallstones as a side effect. Semaglutide has the longer record, including a large heart-outcomes trial in people without diabetes.
- Does Wegovy protect the heart more than Mounjaro?
- Semaglutide 2.4 mg reduced major cardiovascular events by 20% against placebo in the SELECT trial of about 17,600 people with overweight or obesity and existing cardiovascular disease. Tirzepatide does not yet have an equivalent published placebo-controlled outcomes trial in that population, so the two cannot be compared directly on heart outcomes.
- Can you switch from Wegovy to Mounjaro?
- Switching is a prescribing decision. The licences do not set out a switching schedule, and a prescriber decides the starting dose and timing based on the person and their response. It is not something to do without one.
- Which can you get on the NHS in England?
- Both, with conditions. Wegovy is recommended by NICE within specialist weight-management services for up to two years (TA875). Tirzepatide is recommended under TA1026 with access phased in by clinical priority from 2025. Eligibility depends on BMI and weight-related conditions, and a GP can explain the local position.
- Do you regain weight after stopping either one?
- Yes, in the trials. Withdrawal studies showed roughly half (tirzepatide, SURMOUNT-4) to two-thirds (semaglutide, STEP 1 extension) of the lost weight returning within about a year of stopping. Our article on stopping GLP-1 medicines covers the data.
The studies and sources behind this page
Related reading
Educational content only. Not medical advice, diagnosis or treatment. Always consult a qualified healthcare professional before changing your health regimen.