Do semaglutide and tirzepatide have different side-effect profiles?

Step 1, understand what both medicines have in common

A question our prescribers hear most weeks is some version of: "which one is easier on the stomach?" The truthful starting point is that semaglutide (Wegovy) and tirzepatide (Mounjaro) produce near-identical lists of common side effects. Nausea, vomiting, diarrhoea, constipation, reflux and fatigue feature prominently in the patient information for both, and for the same mechanical reason: they both slow gastric emptying and dampen appetite signals through GLP-1 receptor activity. You can read the NHS patient pages for semaglutide and tirzepatide side by side and the lists look strikingly alike.

Both medicines carry a Black Triangle (▼) designation from the MHRA, meaning additional monitoring is ongoing. Both also carry a known (though infrequent) risk of acute pancreatitis; the MHRA issued a Drug Safety Update in January 2026 specifically flagging this for GLP-1 medicines as a class. Severe, persistent stomach pain that spreads to the back warrants urgent medical attention regardless of which medicine you are taking.

The side effects that do appear are most pronounced after starting treatment or after a dose increase, and many people find they settle considerably within the first two weeks. That pattern holds for both drugs. See our broader look at the Wegovy and Mounjaro side-effect comparison for a fuller breakdown of each medicine's licensed schedule.

Step 2, spot where the data diverge

Tirzepatide is a dual GIP and GLP-1 receptor agonist, which means it activates a second gut-hormone pathway that semaglutide does not. That additional mechanism is largely responsible for tirzepatide's stronger average weight-loss results in trials, and it may also account for some differences in the side-effect pattern, though the clinical significance of those differences is modest.

In the SURMOUNT-1 trial, published in the New England Journal of Medicine, nausea was reported in roughly 31–39% of participants across tirzepatide doses, compared with around 44% in STEP 1 for semaglutide 2.4mg. Diarrhoea rates were broadly similar across both trials; constipation appeared somewhat more frequently with tirzepatide at higher doses. These are indirect comparisons (the trials enrolled different populations under different conditions) so they should be treated as indicative, not definitive.

The SURMOUNT-5 head-to-head trial did show that tirzepatide produced greater average weight reduction than semaglutide 2.4mg over 72 weeks, but it was not designed primarily as a side-effect comparison. The tolerability data from that trial did not establish a clear winner on the safety front. For anyone interested in how the two medicines compare on results as well as tolerability, our page on the tirzepatide versus semaglutide side-effect comparison goes into the trial data in more detail.

Step 3, read the comparison table before drawing conclusions

The table below summarises what the trial evidence and UK regulatory sources show. Numbers are drawn from SURMOUNT-1 (tirzepatide) and STEP 1 (semaglutide 2.4mg) (both published in the New England Journal of Medicine) and should be read as approximate rates from separate trials, not as direct head-to-head figures.

The figures suggest semaglutide may produce slightly higher nausea and vomiting rates at the 2.4mg maintenance dose, while tirzepatide can produce more constipation at its highest doses. Neither pattern is dramatic enough to call one medicine categorically easier to tolerate, individual variation matters more than trial averages for most people. You can explore a deeper look at these numbers on our tirzepatide and semaglutide side-effects page.

Worth noting: Wegovy now has an approved 7.2mg maintenance dose in the UK, and the tolerability data at that higher dose are still accumulating. Any comparison with tirzepatide's highest 15mg dose at the 7.2mg semaglutide level is preliminary. Our page covering whether Wegovy has fewer side effects than Mounjaro addresses this evolving picture.

Step 4, what this means in practice, and how a prescriber uses it

Trial percentages are useful context. They are not a prediction for any individual. A person who tolerated semaglutide poorly may do better on tirzepatide, or vice versa, and there is no reliable way to know in advance without trying. That is exactly why these are prescription-only medicines rather than items you can choose from a shelf.

A prescriber will weigh your medical history, any other medicines you take, your previous experience with GLP-1 treatment if relevant, and your own preferences before recommending one over the other. The Wegovy versus Mounjaro overview covers how the two medicines compare more broadly, including on results and cost context. For a sense of how pricing differs between them, the cost comparison page has the detail.

At nume, every consultation is read by a real prescriber, not a decision algorithm. If tolerability is a concern for you, that conversation belongs in the consultation. It is also worth knowing that both treatments are started at the lowest dose precisely to give your system time to adjust, and titration is managed by your prescriber based on how you respond. Check your eligibility to start that conversation.