Retatrutide, tirzepatide and semaglutide compared: efficacy and side effects

The decision you are actually making right now

If you have landed on this page weighing up retatrutide alongside the two licensed options, the first thing worth knowing is that the comparison is partly hypothetical. Retatrutide is a triple receptor agonist, targeting GIP, GLP-1 and glucagon pathways simultaneously. Phase 2 trial results, published in the New England Journal of Medicine in 2023, reported an average weight reduction of around 24% over 48 weeks at the highest dose tested, figures that attracted considerable attention. But phase 3 trials were still under way as of mid-2026, and no regulatory submission had been accepted by the MHRA. It is not available on prescription in the UK.

That leaves two licensed choices. Tirzepatide (Mounjaro), a dual GIP and GLP-1 receptor agonist made by Eli Lilly, is the only dual-agonist weight-loss medicine approved in the UK. Semaglutide (Wegovy), a GLP-1 receptor agonist made by Novo Nordisk, was the first of the modern weight-loss injections to receive UK approval. Both are licensed for weight management alongside lifestyle changes in adults with a BMI of 30 or above, or 27 or above with at least one weight-related condition. The practical question is which fits your health picture, and that is a clinical call, not a headline comparison.

What the trial data actually show about efficacy

Head-to-head evidence between tirzepatide and semaglutide now exists. The SURMOUNT-5 trial, published in the New England Journal of Medicine in 2025, enrolled 751 adults with obesity and no diabetes and ran for 72 weeks. Tirzepatide at its highest tolerated dose produced a greater average weight reduction than semaglutide 2.4mg. NICE's appraisal of tirzepatide (TA1026) also noted that indirect comparisons favoured tirzepatide. The SURMOUNT-1 trial recorded average body-weight reductions of around 20–21% at 15mg over 72 weeks. The STEP 1 trial for semaglutide 2.4mg showed an average reduction of approximately 15% over 68 weeks.

For retatrutide, the phase 2 figures are striking, but phase 2 studies recruit hundreds of participants, not thousands, and the doses, titration schedules and populations may shift in phase 3. Comparing a phase 2 result against phase 3 results from two separate trials is a reasonable starting point for curiosity, it is not a reliable basis for a personal decision. The table below summarises what the published data show, with the important caveats about study design.

Sources: SURMOUNT-1 and STEP 1, New England Journal of Medicine; NICE TA1026; phase 2 retatrutide data, NEJM 2023. All figures are trial averages; individual results vary.

Side effects across the three: what is similar and what differs

Gastrointestinal effects dominate across all three. Nausea, vomiting, diarrhoea and constipation are the most commonly reported events with both licensed medicines, typically most noticeable in the early weeks of treatment or after a dose increase, then settling for most people. A detailed comparison of the gastrointestinal profiles of tirzepatide and semaglutide is worth reading if this is a specific concern. Retatrutide's phase 2 data showed a broadly similar GI-led profile, with nausea being the most frequent adverse event.

The MHRA's January 2026 Drug Safety Update highlighted acute pancreatitis as a known but infrequent risk with GLP-1 class medicines: severe, persistent stomach pain that may spread to the back, with or without vomiting, should prompt urgent medical attention. If you want to understand how the two licensed medicines sit alongside each other on this and other safety signals, our tirzepatide vs semaglutide side effects comparison covers the published data in detail. The MHRA Yellow Card scheme is where patients report suspected side effects from any licensed medicine.

One habit worth building before starting treatment: check the patient information leaflet that comes with your pen. Running your eye down the listed common side effects takes under a minute and tells you exactly what to watch for in the first few weeks. Our prescribers also go through this at aftercare, but having the leaflet to hand is practical insurance.

For a closer look at how the two licensed options compare on tolerability, our page on whether semaglutide has fewer side effects than tirzepatide covers the nuance in detail, including the contraception interaction specific to tirzepatide that does not have equivalent evidence for semaglutide.

Which licensed option suits you, and how the consultation resolves it

Tirzepatide and semaglutide share a licensing framework for weight management but differ in mechanism, average trial results and some aspects of their side-effect profiles. Mounjaro's dual-agonist mechanism and the SURMOUNT-5 head-to-head evidence make it the current frontrunner on average weight reduction. Wegovy has a longer clinical track record in the UK, a well-established titration pathway, and now extends to a 7.2mg maintenance dose for people who need it. Many people also find it helpful to read about the side effects of tirzepatide vs semaglutide before deciding which direction to take into a consultation. A full comparison of Wegovy and Mounjaro sets out the key differences if you want more detail before a consultation.

Both are prescription-only medicines. A prescriber considers your full health picture (existing conditions, other medicines, your goals, and how you respond over time) before recommending one over the other. If you are also weighing up tirzepatide against an Ozempic prescription you may already hold, our page covering tirzepatide vs Ozempic side effects is a useful reference point before speaking to a prescriber. Retatrutide, however well it eventually performs in phase 3, cannot be part of that conversation in the UK yet. Waiting for it when licensed options are already available is a personal calculation, but it is worth making that calculation clearly rather than by accident.

Our clinical team, introduced on our clinical team page, reviews every consultation personally. Which of the two licensed medicines suits you is a decision made with a prescriber who knows your case, not one made by a comparison table. Check your eligibility and start a free consultation today.