Tirzepatide in the UK: The Science Behind Mounjaro

Tirzepatide is the active ingredient in Mounjaro, a once-weekly injection made by Eli Lilly. It is the first medicine licensed in the UK that activates two gut hormone receptors at once, GIP and GLP-1, and it is authorised by the MHRA both for type 2 diabetes and for weight management in eligible adults. NICE recommends it for obesity on the NHS under technology appraisal TA1026, and it is also prescribed privately. This guide explains the science: what the molecule is, how it works, what the major trials found, how it is regulated in the UK, and what is still unknown.

What is tirzepatide?

The molecule

Tirzepatide is a peptide made up of 39 amino acids. Its structure is based on the natural hormone GIP (glucose-dependent insulinotropic polypeptide), but it has been engineered so that it also activates the receptor for GLP-1 (glucagon-like peptide-1).

Natural GIP and GLP-1 are broken down within minutes in the bloodstream. To make a weekly medicine, the molecule was modified in two key ways:

• Changes to its amino-acid sequence that make it resistant to the enzyme DPP-4, which normally breaks down these hormones.
• A fatty acid side chain that allows it to bind to albumin, a protein in the blood. This slows its removal by the kidneys and keeps it in circulation for longer.

The result, according to the UK Summary of Product Characteristics (SmPC), is a half-life of approximately five days. That is long enough for once-weekly injection, with steady levels building up over the first few weeks of treatment.

A "dual agonist"

An agonist is a substance that activates a receptor. Tirzepatide activates two:

• The GIP receptor, found in the pancreas, fat tissue and the brain.
• The GLP-1 receptor, found in the pancreas, gut, brain, heart and other tissues.

Laboratory studies suggest tirzepatide activates the GIP receptor with an affinity similar to natural GIP, while its activity at the GLP-1 receptor is weaker than natural GLP-1. Researchers describe this as an "imbalanced" agonist, weighted towards GIP. Exactly how this balance contributes to its clinical effects is still being researched.

For an overview of the medicine as it is used in the UK, see our Mounjaro hub. For a plain-English walkthrough of the mechanism, see our guide on how Mounjaro works, and for the wider medicine class, what GLP-1 medications are.

How tirzepatide works in the body

Appetite and food intake

The main way tirzepatide leads to weight loss is by reducing appetite and food intake. GLP-1 receptors in the brain, particularly in areas such as the hypothalamus and brainstem that regulate hunger and fullness, are a key target. People taking tirzepatide often describe:

• Feeling full sooner and for longer.
• Less hunger between meals.
• Fewer intrusive thoughts about food, sometimes called "food noise".

GIP receptors are also present in brain areas involved in appetite, and animal studies suggest GIP may add to the appetite effects and may reduce nausea signalling. How much these findings apply to humans is not yet fully established.

Stomach emptying

GLP-1 activity slows the rate at which food leaves the stomach. This contributes to feeling full, but also to side effects such as nausea, bloating and reflux. This effect tends to lessen over time with continued treatment. It is also why anaesthetists need to know if you are taking tirzepatide before a procedure; see our guide to GLP-1 medication before surgery and anaesthesia.

Blood sugar

Both GIP and GLP-1 are "incretins": hormones released from the gut after eating that boost insulin release from the pancreas. Crucially, they do this in a glucose-dependent way, meaning they mainly increase insulin when blood sugar is raised. GLP-1 also reduces glucagon, a hormone that raises blood sugar. This explains why tirzepatide lowers blood sugar effectively in type 2 diabetes but rarely causes hypoglycaemia on its own.

Fat tissue and metabolism

GIP receptors in fat tissue may influence how fat is stored and handled. Researchers are investigating whether this contributes to tirzepatide's effects on body composition, blood fats and insulin sensitivity. This is an area of active research rather than settled science.

The trial evidence

Tirzepatide has been studied in two main clinical trial programmes: SURPASS, in type 2 diabetes, and SURMOUNT, in obesity and overweight. Other trials have looked at specific conditions such as sleep apnoea and heart failure.

SURMOUNT: weight management

The table below summarises the key weight management trials. Figures are average percentage changes in body weight; they are rounded and come from the trials' published primary analyses.

SURMOUNT-1 in more detail

SURMOUNT-1 enrolled more than 2,500 adults and was the pivotal trial for the weight management licence. As well as average weight loss, it reported the proportion of people reaching different thresholds. On the higher doses, a large majority lost at least 5% of their body weight, and a substantial proportion lost 20% or more. Improvements were also seen in waist circumference, blood pressure, blood fats and markers of blood sugar control.

It is important to remember that these are averages. In every trial, some people lost much more weight and some much less. Our guide to Mounjaro results over time explores the range of responses, and realistic weight loss expectations puts the numbers in context.

What happens when treatment stops: SURMOUNT-4

SURMOUNT-4 is one of the most important trials for understanding tirzepatide as a long-term treatment. All participants took tirzepatide for 36 weeks and lost on average about a fifth of their body weight. They were then randomised to continue tirzepatide or switch to placebo. Those who continued lost further weight, while those switched to placebo regained a substantial proportion of what they had lost over the following year.

This supports the view, reflected in NICE guidance, that obesity is a chronic condition and that the benefits of treatment depend on continuing it. See Mounjaro maintenance and weight regain after stopping.

Head to head with semaglutide: SURMOUNT-5

SURMOUNT-5, published in the New England Journal of Medicine in 2025, compared the maximum tolerated dose of tirzepatide (10mg or 15mg) with the maximum tolerated dose of semaglutide (1.7mg or 2.4mg) in adults with obesity but without diabetes. Over 72 weeks, average weight loss was about 20% with tirzepatide and about 14% with semaglutide. Gastrointestinal side effects were common with both. The trial was open-label and funded by Eli Lilly. Our detailed guide to SURMOUNT-5 covers the design and limitations.

SURPASS: type 2 diabetes

The SURPASS programme compared tirzepatide with placebo and with other diabetes medicines, including semaglutide 1mg (SURPASS-2), insulin degludec (SURPASS-3) and insulin glargine (SURPASS-4). Across these trials, tirzepatide produced larger reductions in HbA1c (a measure of long-term blood sugar) and in body weight than the comparators. A cardiovascular outcomes trial comparing tirzepatide with dulaglutide in people with type 2 diabetes, SURPASS-CVOT, has also reported; readers should check the latest publications for its detailed findings.

NICE recommends tirzepatide for type 2 diabetes under TA924 (October 2023), in specific circumstances after other treatments. See our guide to GLP-1 medication and type 2 diabetes.

Beyond weight: other conditions

• Obstructive sleep apnoea. In SURMOUNT-OSA (NEJM, 2024), tirzepatide reduced the apnoea-hypopnoea index, a measure of sleep apnoea severity, by roughly half or more compared with small changes on placebo, in people with obesity and moderate-to-severe sleep apnoea. See tirzepatide and obstructive sleep apnoea.
• Heart failure with preserved ejection fraction. In SUMMIT (NEJM, 2025), people with obesity and this type of heart failure had a lower risk of cardiovascular death or worsening heart failure events on tirzepatide than on placebo, alongside better symptoms and exercise capacity.
• Liver disease. Phase 2 research has studied tirzepatide in metabolic dysfunction-associated steatohepatitis (MASH). Larger trials are needed.

Whether these findings lead to changes in the UK licence is a matter for the MHRA. At the time of writing, check the current SmPC for licensed indications.

Body composition

Concerns are often raised about muscle loss with weight-loss medicines. In a body-composition substudy of SURMOUNT-1 using DXA scanning, around three-quarters of the weight lost on tirzepatide was fat and around a quarter was lean mass. That ratio is broadly similar to what is seen with other forms of weight loss. Lean mass includes muscle but also water and organ tissue, so it is not a direct measure of muscle. Strength training and adequate protein are widely recommended; see preserving muscle on GLP-1 treatment.

A short history of tirzepatide

The idea of combining gut hormones to treat diabetes and obesity grew out of decades of research on incretins. GLP-1 receptor agonists such as exenatide and liraglutide were developed first, and semaglutide followed. GIP was long thought to be less useful as a drug target, because its effect on insulin appeared blunted in type 2 diabetes. Researchers later found that combining GIP and GLP-1 activity in a single molecule could produce larger effects on blood sugar and weight than GLP-1 activity alone, at least in early studies.

Key milestones include:

Tirzepatide is sometimes described as the first of a new generation of "multi-agonist" medicines. Others in development combine GLP-1 with glucagon or amylin activity. See the GLP-1 pipeline for an overview of what is being studied.

How tirzepatide is given

Mounjaro is injected under the skin (subcutaneously) once a week, on the same day each week, at any time of day, with or without food. The SmPC lists the abdomen, thigh and upper arm as injection sites, and advises rotating the site with each dose. If needed, the injection day can be changed as long as there are at least three days (72 hours) between doses.

If a dose is missed, the SmPC says it should be taken as soon as possible within four days; if more than four days have passed, the missed dose should be skipped and the next one taken on the usual day. See missed Mounjaro doses and our KwikPen guide for practical detail. Pens are stored in the fridge, with a limited period allowed at room temperature, as explained in storing and travelling with Mounjaro.

Safety and side effects

Common side effects

According to the UK SmPC, the most common side effects are gastrointestinal: nausea, diarrhoea, constipation, vomiting, indigestion and abdominal pain. These are most frequent during dose escalation and usually ease over time. Other reported effects include reduced appetite, tiredness, injection-site reactions, hair loss and, in people with diabetes taking insulin or sulfonylureas, low blood sugar.

Warnings

The SmPC includes warnings about:

• Acute pancreatitis, which is rare but serious.
• Gallbladder problems, including gallstones, which are linked to rapid weight loss.
• Dehydration and kidney problems, usually following significant vomiting or diarrhoea.
• Diabetic retinopathy in people with diabetes, where rapid improvement in blood sugar may temporarily worsen eye disease.
• Aspiration under anaesthesia, because of delayed stomach emptying.
• Reduced effectiveness of oral contraceptives, with advice to use a barrier or non-oral method for four weeks after starting and after each dose increase.

Tirzepatide should not be used in pregnancy, and the MHRA has reminded patients and prescribers about this. Our Mounjaro side effects guide covers these in detail, and who shouldn't take GLP-1 medications explains contraindications.

Tirzepatide in the UK: regulation and access

Licensing

The Medicines and Healthcare products Regulatory Agency (MHRA) authorised Mounjaro for type 2 diabetes first, and extended the licence to weight management in November 2023. For weight management, it is licensed for adults alongside a reduced-calorie diet and increased physical activity, with:

• A body mass index (BMI) of 30 kg/m² or more, or
• A BMI of 27 to under 30 kg/m² with at least one weight-related condition, such as high blood pressure, type 2 diabetes, abnormal blood fats, obstructive sleep apnoea or cardiovascular disease.

Dosing

Mounjaro is supplied in the UK as a KwikPen containing four weekly doses. Treatment starts at 2.5mg once weekly for four weeks, then increases in 2.5mg steps, with at least four weeks at each dose, up to a maximum of 15mg. The usual maintenance doses for weight management are 5mg, 10mg or 15mg. Our guide to Mounjaro doses has the full schedule.

NICE and the NHS

NICE technology appraisal TA1026, published in December 2024, recommends tirzepatide for managing overweight and obesity on the NHS for adults with:

• An initial BMI of at least 35 kg/m², and
• At least one weight-related comorbidity.

Lower BMI thresholds, usually reduced by 2.5 kg/m², apply to people from South Asian, Chinese, other Asian, Middle Eastern, Black African or African-Caribbean backgrounds. NICE advises stopping treatment if less than 5% of initial weight has been lost after six months on the highest tolerated dose.

Because so many people are potentially eligible, NHS England published interim commissioning guidance setting out a phased rollout. Integrated care boards were required to fund access in primary care from 23 June 2025, with the first phase prioritising people with the highest BMI and multiple weight-related conditions. The rollout is planned over several years, and access varies by area. Our guide to Mounjaro on the NHS explains the criteria and phases.

Private prescribing

Many people in the UK receive Mounjaro through private prescribers, including online pharmacies and clinics regulated by the General Pharmaceutical Council (GPhC) or Care Quality Commission (CQC). A private prescriber must still assess whether treatment is clinically appropriate and within the licence, including checking BMI and medical history.

The cost of private treatment depends on factors such as dose, the provider's service model and what follow-up is included. Eli Lilly raised the UK list price of Mounjaro for private supply from September 2025, which affected what many private providers charge. We do not quote prices in our guides because they change frequently; see our prices page for current comparisons and our provider comparison for how services differ.

Unlicensed and falsified products

The MHRA has warned the public about unlicensed tirzepatide sold online, including products labelled "for research use only", and about falsified pens. These products have not been checked for quality, dose or sterility. In the UK, the licensed tirzepatide product is Mounjaro, supplied on prescription by a registered pharmacy. Our guide to fake and unlicensed weight-loss jabs explains the warning signs.

Tirzepatide compared with other options

For direct comparisons, see Mounjaro vs Wegovy, Mounjaro vs oral GLP-1 tablets, and our overview of semaglutide in the UK.

What we still don't know

• Long-term outcomes in obesity. A large cardiovascular outcomes trial in people with obesity (SURMOUNT-MMO) is under way. Until it reports, the effect of tirzepatide on heart attacks, strokes and death in people without diabetes is not established in the same way as it is for semaglutide in the SELECT trial.
• Very long-term safety. Trials have followed people for around one to three years. Experience over decades is limited.
• The ideal approach to maintenance. It is not yet clear whether lower doses, less frequent dosing or other strategies can maintain weight loss for most people.
• Who responds most. Response varies widely, and there are no reliable tests to predict it.

When to speak to a professional

Speak to your GP, pharmacist or a regulated prescriber if you are considering tirzepatide. They will check your BMI, medical history and other medicines, and discuss whether it is suitable and safe for you.

Tell your prescriber before starting if you have had pancreatitis, gallbladder disease, severe stomach or bowel problems, diabetic eye disease, kidney problems, an eating disorder, or if you are pregnant, planning pregnancy or breastfeeding.

During treatment, contact your prescriber promptly if side effects stop you eating or drinking, or if you notice changes in mood.

Seek urgent medical help (NHS 111, or 999 / A&E in an emergency) if you have:

• Severe, persistent abdominal pain, which may spread to your back, with or without vomiting.
• Pain in the upper right abdomen, fever, or yellowing of the skin or eyes.
• Signs of severe dehydration, such as confusion or passing very little urine.
• Signs of a serious allergic reaction, such as swelling of the face or throat, or difficulty breathing.
• Sudden changes in vision if you have diabetes.

Prescribing decisions belong to your prescriber, who can weigh the benefits and risks for you as an individual.