Tirzepatide vs Semaglutide: What the Head-to-Head SURMOUNT-5 Trial Found

In short: SURMOUNT-5, published in the New England Journal of Medicine in 2025, was the first large trial to compare tirzepatide (brand name Mounjaro) directly with semaglutide (brand name Wegovy) for weight management. Over 72 weeks, adults with obesity lost on average 20.2% of their body weight with tirzepatide and 13.7% with semaglutide. The trial was open-label and funded by the maker of tirzepatide, results varied widely between people, and the best choice for any individual depends on a clinical assessment.

This summary, written by a Ready Health prescribing pharmacist, explains what the trial did and did not show, and what it means if you are considering medical weight management.

What was the SURMOUNT-5 trial?

SURMOUNT-5 was a randomised, open-label phase 3b trial carried out in the United States and Puerto Rico. Key features:

• 751 adults with obesity (BMI 30 or more), or BMI 27 or more with at least one weight-related condition
• participants did not have type 2 diabetes
• everyone received advice on a reduced-calorie diet and physical activity
• participants were given weekly injections of either tirzepatide (maximum tolerated dose of 10 mg or 15 mg) or semaglutide (maximum tolerated dose of 1.7 mg or 2.4 mg) for 72 weeks

What were the results?

Tirzepatide also led to a greater average reduction in waist circumference. The most common side effects with both medicines were digestive, such as nausea, constipation, diarrhoea and vomiting, and were mostly mild to moderate and most frequent during dose increases.

Why might tirzepatide lead to more weight loss?

Semaglutide acts on the GLP-1 receptor, while tirzepatide acts on both the GLP-1 and GIP receptors. Researchers think this dual action may explain the larger average effect on appetite and weight, although the exact mechanism is still being studied. You can read more in our guides on how tirzepatide works and how semaglutide works.

What are the limitations of the trial?

• Open-label design: participants and researchers knew which medicine was being given, which can influence some outcomes.
• Industry funding: the study was funded by Eli Lilly, the manufacturer of tirzepatide.
• Population: it was carried out in the US and Puerto Rico in people without type 2 diabetes, so results may differ in other groups.
• Doses: it compared the doses available at the time. A higher 7.2 mg weekly dose of semaglutide has since been approved by the MHRA (January 2026) for adults with a BMI of 30 or more, and this was not part of SURMOUNT-5.
• Averages hide variation: some people lose more weight on semaglutide than others do on tirzepatide, and some people cannot tolerate one or the other.

What does this mean for patients in the UK?

Both medicines are licensed in the UK for weight management alongside diet and physical activity, and both are recommended by NICE for specific groups on the NHS. Trial averages are only one part of the decision. A prescriber will also consider your medical history, other conditions and medicines, how you have tolerated previous treatment, pregnancy plans and your own preferences. Daily tablets are now also licensed in the UK, which widens the options to discuss.

Both medicines carry the same important safety advice, including MHRA warnings on acute pancreatitis and on contraception, and neither should be used in pregnancy or while breastfeeding.

Frequently asked questions

Is tirzepatide better than semaglutide?

In SURMOUNT-5, average weight loss was greater with tirzepatide. That does not mean it is the right choice for everyone; suitability depends on an individual assessment.

Were side effects different between the two?

Side effects were similar in type, mainly digestive. Slightly fewer people stopped tirzepatide than semaglutide because of digestive side effects.

Can I switch from one to the other?

Yes, with a prescriber's plan. The new medicine is usually started at its lowest dose. See our guide on switching from tirzepatide to semaglutide.

Did the trial include people with type 2 diabetes?

No. People with type 2 diabetes were excluded, so results may differ for them.

Key takeaways

• SURMOUNT-5 compared tirzepatide and semaglutide head-to-head over 72 weeks.
• Average weight loss was 20.2% with tirzepatide and 13.7% with semaglutide.
• The trial was open-label, industry-funded and did not include the newer 7.2 mg semaglutide dose.
• Individual responses vary, so treatment decisions should be made with a prescriber.

Sources and further reading

• American College of Cardiology: SURMOUNT-5 journal scan
• NICE TA1026: tirzepatide for managing overweight and obesity
• NICE TA875: semaglutide for managing overweight and obesity
• MHRA: approval of the 7.2 mg semaglutide dose

Last reviewed: October 2026 by Shamir Patel, Independent Prescribing Pharmacist, Ready Health. This article is general information and does not replace advice from your own clinician. Brand names are trademarks of their respective owners.

If you would like to discuss your weight-management options, you can book a weight-management consultation at Ready Health in Standish, Wigan. A prescriber will assess your health and decide with you whether any medicine is suitable.