GLP-1 and Mounjaro: how tirzepatide works and what the trial data shows

What the SURMOUNT trials established about tirzepatide's GLP-1 action

The first thing to understand is that GLP-1 (glucagon-like peptide-1) is a hormone your gut releases after eating. It signals to your brain that food has arrived, slows the speed at which your stomach empties, and helps regulate blood sugar. If you want a fuller picture of how this works in practice, you can read about how GLP-1 and tirzepatide interact as a treatment approach, which explains why the whole class tends to reduce appetite and food intake.

Tirzepatide, sold in the UK as Mounjaro by Eli Lilly, was studied in the SURMOUNT programme across thousands of adults. SURMOUNT-1 randomised 2,539 participants without diabetes and tracked them for 72 weeks. At the 15mg dose, average body-weight reduction was around 20–21%. The New England Journal of Medicine published the full results, and NICE cited this data in its appraisal of tirzepatide (TA1026, December 2024) when recommending it for adults with a BMI of 35 or above alongside at least one weight-related condition.

The SURMOUNT-5 trial then ran tirzepatide head-to-head against semaglutide 2.4mg (Wegovy). Over 72 weeks, tirzepatide produced greater average weight loss, the first direct comparison of these two medicines in adults with obesity. Those results matter because they move the conversation from trial-versus-trial estimates to a direct, controlled test. You can read what tirzepatide's clinical record looks like in full for a more detailed look at how the numbers break down across doses.

The GIP receptor: what makes Mounjaro different from other GLP-1 medicines

Standard GLP-1 medicines (semaglutide, liraglutide) bind to one receptor. Mounjaro binds to two: GLP-1 and GIP (glucose-dependent insulinotropic polypeptide). GIP is released earlier in the digestive process, before food fully enters the small intestine, and it works alongside GLP-1 on appetite centres in the brain and on fat tissue directly.

The dual mechanism is why researchers expected tirzepatide to produce stronger effects than single-agonist medicines, and the trial data broadly confirmed that expectation. Whether it's the right choice for any individual is a different question, one that depends on medical history, other medicines, and personal preferences about how the treatment is taken. A good place to start that conversation is this explanation of the GLP-1 and GIP combination in Mounjaro, which goes deeper into the receptor science.

One practical point worth knowing: because tirzepatide slows gastric emptying, it can affect the absorption of oral medicines taken at the same time, including the contraceptive pill. Women taking combined or progestogen-only oral contraceptives are advised to add a barrier method for the first four weeks of treatment and for four weeks after each dose increase. NHS England's guidance on weight-management injections covers this clearly and is worth reading before you start.

Who Mounjaro is licensed for, and the BMI thresholds that apply

The UK licence covers adults managing weight alongside a reduced-calorie diet and increased physical activity. Two BMI starting points apply: 30 or above, or 27 or above when at least one weight-related condition is present, for example, high blood pressure, dyslipidaemia, obstructive sleep apnoea, or type 2 diabetes. Lower thresholds apply for some ethnic backgrounds under UK guidance, with NICE specifying a 2.5 kg/m² reduction for South Asian, Chinese, Middle Eastern, Black African, or African-Caribbean backgrounds.

Mounjaro is also licensed for type 2 diabetes, and if you're weighing up whether it suits your situation, it helps to understand what Mounjaro's GLP-1 mechanism means for how the medicine works day to day. These are separate indications; the dosing schedules begin at the same 2.5mg starting strength, but the clinical rationale and monitoring differ. If you're looking at the cost side of treatment, a breakdown of what UK Mounjaro pricing actually covers sets out what a legitimate private prescription includes and why quoted prices vary between providers.

The NHS route to tirzepatide is now open under NICE TA1026 but is being phased in gradually from June 2025, starting with people who have a BMI of 40 or above and at least four of five specified conditions. A second cohort, covering BMI 35–39.9 with four or more conditions, became eligible in June 2026. Meeting the NICE criteria doesn't guarantee a short wait, which is why private prescription through a regulated pharmacy remains the faster route for many people who qualify medically but aren't yet in scope for NHS access.

Side effects, safety monitoring, and one quick check worth doing

The most commonly reported side effects are gastrointestinal: nausea, diarrhoea, constipation, reflux, and burping tend to be most noticeable in the early weeks or after a dose step. They are generally described as mild to moderate and settle for most people within days to a couple of weeks. The NHS's tirzepatide information page carries a plain-English rundown of the full side-effect profile, and is a reliable reference.

On the serious-but-rare end, the MHRA highlighted acute pancreatitis in a January 2026 Drug Safety Update for GLP-1 medicines. Severe stomach pain that spreads to the back (with or without vomiting) needs prompt medical attention rather than waiting to see if it resolves. Gallbladder symptoms and signs of dehydration from prolonged vomiting or diarrhoea are also reasons to contact a clinician rather than manage at home.

One simple check that takes less than a minute: if you're buying or considering buying from any online pharmacy, pull up the GPhC register at pharmacyregulation.org and confirm the premises registration number is listed. A legitimate UK pharmacy has one. Sellers offering these medicines without a prescription are a red flag flagged by the MHRA, and fake pens have caused hospitalisations. The common questions about the Mounjaro injection page covers what a genuine KwikPen should look like and how to store it properly.

Mounjaro is not recommended during pregnancy, while breastfeeding, or when trying to conceive. It is not licensed for under-18s. People with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 should discuss this with a prescriber before starting.

If you'd like to talk through whether Mounjaro is appropriate for your situation, check your eligibility through a free consultation with our GPhC-registered prescribers at nume.