Tirzepatide vs semaglutide: the difference explained

Asked plainly, the tirzepatide vs semaglutide difference is this: semaglutide acts on one gut-hormone receptor, GLP-1, and tirzepatide acts on two, GIP and GLP-1. Semaglutide is the molecule in the Wegovy injection, the Wegovy pill, Ozempic and Rybelsus; tirzepatide is the molecule in Mounjaro. Both are UK prescription-only medicines given as a once-weekly injection for weight management, and one trial in adults with obesity, SURMOUNT-5, has compared them directly.

This is information only, not medical advice; a prescriber decides whether either is suitable.

Tirzepatide vs semaglutide: what the two molecules are

GLP-1 and GIP are gut hormones released after a meal; both medicines are long-acting, laboratory-made molecules that switch on those receptors, which allows a weekly injection.

Semaglutide is a GLP-1 analogue sharing 94% of its sequence with human GLP-1; it selectively activates the GLP-1 receptor, acting on appetite centres in the brain and slowing stomach emptying.

Tirzepatide is described in its SmPC as “a long acting GIP and GLP-1 receptor agonist” with high affinity for both receptors: its activity at the GIP receptor is similar to the natural hormone's, and at the GLP-1 receptor lower than natural GLP-1. For the shared mechanism, see how GLP-1 drugs cause weight loss.

Which UK products contain which

“Semaglutide” alone does not say which product or dose is meant, and a diabetes brand is not a weight-loss licence (see GLP-1 for diabetes vs weight loss).

How they are taken and dosed

Both are injected under the skin once a week, at any time of day, with or without food, into the abdomen, thigh or upper arm (Mounjaro: upper arm only if someone else injects). Both start low and climb, because digestive effects peak just after a dose increase.

• Semaglutide (Wegovy): 0.25 mg weekly for four weeks, then 0.5, 1 and 1.7 mg for four weeks each, reaching the 2.4 mg maintenance dose from week 17. Adults with obesity may go on to 7.2 mg after at least four weeks on 2.4 mg (authorised in January 2026).
• Tirzepatide (Mounjaro): 2.5 mg weekly for four weeks as a starter dose, then 5 mg, rising in 2.5 mg steps after at least four weeks at each, to a maximum of 15 mg. Maintenance is 5, 10 or 15 mg.

Both SmPCs call for a review if under 5% of starting weight has gone after six months (for Mounjaro, six months after reaching the highest tolerated dose). Semaglutide's daily tablet is covered in GLP-1 tablets vs injections.

What the separate trials showed

In STEP 1 (semaglutide 2.4 mg, 68 weeks) mean weight change was −14.9% against −2.4% on placebo. In SURMOUNT-1 (tirzepatide, 72 weeks) it was −16.0% at 5 mg, −21.4% at 10 mg and −22.5% at 15 mg against −2.4%. Both enrolled adults without type 2 diabetes, but different participants, durations and procedures make cross-trial figures an unfair ranking.

SURMOUNT-5: the head-to-head trial

SURMOUNT-5, published in the New England Journal of Medicine in 2025, is the only randomised head-to-head trial of the two for obesity. It followed 751 adults with obesity, or overweight with a weight-related complication, but without type 2 diabetes, for 72 weeks on the highest dose each could tolerate: tirzepatide 10 or 15 mg, or semaglutide 1.7 or 2.4 mg.

At week 72 the mean change in weight was −20.2% with tirzepatide and −13.7% with semaglutide in the published analysis (everyone who had at least one dose); the UK Mounjaro SmPC gives the same endpoint as −21.6% against −15.4% from a different statistical analysis. Waist circumference fell by 18.4 cm against 13.0 cm. People on tirzepatide were more likely to lose at least 10%, 15%, 20% or 25% of their body weight; the manufacturer's announcement put the 25% threshold at 31.6% against 16.1%. The most common adverse events in both groups were gastrointestinal, mostly mild to moderate and during dose escalation.

Three caveats: it was open-label; it was funded by tirzepatide's manufacturer, which said it was not designed to examine differences in adverse events; and the comparator was semaglutide 2.4 mg, not the 7.2 mg dose approved afterwards.

Side effects: the same family

Because both act on the GLP-1 receptor, their side effects overlap heavily: nausea, diarrhoea, vomiting and constipation are common with each, with tiredness listed for both and headache for semaglutide. They cluster around dose increases and are mostly mild to moderate.

The rarer, serious risks are shared too: acute pancreatitis, gallstones, dehydration severe enough to affect the kidneys, and low blood sugar alongside insulin or a sulfonylurea. One label difference: semaglutide's product information warns about NAION, a rare eye condition causing sudden vision loss, which tirzepatide's does not. Both labels caution that rapid improvement in blood-sugar control can temporarily worsen diabetic retinopathy, so those affected should be monitored closely. Neither is for use in pregnancy. Report suspected side effects through the MHRA Yellow Card scheme; see also managing GLP-1 side effects.

Licensed uses and NHS access in the UK

For weight management both licences cover adults with a BMI of 30 or more, or 27 to under 30 with a weight-related condition; Wegovy's also covers adolescents from 12 with obesity, and cardiovascular risk reduction in adults with established cardiovascular disease and a BMI of 27 or more. On the NHS in England, Wegovy is available through specialist weight-management services for up to two years (NICE TA875) and for adults with established cardiovascular disease (TA1152); Mounjaro is being rolled out in phases under TA1026. See who is eligible for GLP-1 treatment in the UK.

Cost, and who decides

Private prices vary between regulated providers. The MHRA advises obtaining these medicines only from a registered pharmacy after a consultation, never from beauty salons or social-media sellers. Which molecule, if either, is appropriate depends on medical history, other medicines, early tolerability and the licence that applies: a prescriber's judgement. See also our comparison page, FAQ and GLP-1 medications compared.

Frequently asked questions

Related reading

• GLP-1 medications compared
• GLP-1 tablets vs injections
• Stopping a GLP-1 medicine