Mounjaro®
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Start journey Learn moreComparing the side-effect evidence: what phase 2 retatrutide data and the SURMOUNT trials tell us
What the phase 2 retatrutide trial reported on tolerability
The phase 2 retatrutide trial (published in The Lancet, 2023) enrolled 338 adults without diabetes across multiple dose groups over 24 weeks. Nausea was the most common adverse event, reported by roughly half of participants in the higher-dose groups, with vomiting and diarrhoea also frequent. Importantly, most events were mild to moderate in severity and peaked in the early weeks of titration before tapering off, a pattern familiar to anyone who has reviewed data for GLP-1 class medicines more broadly. Injection-site reactions were uncommon. Gallbladder-related events were noted at a low rate, consistent with the class. The triple-receptor mechanism (adding glucagon agonism to GIP and GLP-1) is hypothesised to drive slightly greater energy expenditure than dual agonism, but whether that translates into a different safety signal at scale is not yet established; phase 3 data do not yet exist. This is the core limitation of any comparison right now: retatrutide's tolerability profile at the doses and durations relevant to long-term weight management is genuinely unknown.
How tirzepatide's side-effect picture compares after full phase 3 scrutiny
Tirzepatide's profile is substantially better characterised. The SURMOUNT-1 trial randomised 2,539 adults with obesity over 72 weeks, and the full Mounjaro side-effect dataset (including gastrointestinal events, pancreatitis signals and injection-site findings) was scrutinised as part of the MHRA licensing process. Nausea, vomiting, diarrhoea and constipation are the most commonly reported effects, with nausea most likely around dose increases and generally settling within a fortnight. The MHRA issued a Drug Safety Update in January 2026 flagging acute pancreatitis as an infrequent but serious risk across the GLP-1 class: severe, persistent abdominal pain that may radiate to the back warrants urgent medical attention. That signal applies to all medicines in this class, including any future retatrutide product. The NHS tirzepatide patient information page provides a clear summary of what side effects to watch for and when to seek help. A question our prescribers hear most weeks is whether the side effects of tirzepatide are worse than those of older GLP-1 medicines, in short, the GI profile is broadly similar to the class, and most people find the first few weeks the most demanding. It is also worth knowing that urinary tract infections have been reported as a side effect of Mounjaro, something prescribers factor in when reviewing your full medical history.
A direct evidence comparison, what is and is not yet known
The table below sets out what the published evidence currently tells us. Bear in mind that the retatrutide figures come from a 24-week phase 2 study, while tirzepatide's come from 72-week phase 3 trials across thousands of participants, the two bodies of evidence are not yet comparable in depth or duration.
| Feature | Retatrutide (phase 2, 2023) | Tirzepatide / Mounjaro (phase 3, licensed) |
|---|---|---|
| Receptor targets | GIP, GLP-1, glucagon (triple) | GIP, GLP-1 (dual) [Source: MHRA/eMC SmPC] |
| Most common side effects | Nausea, vomiting, diarrhoea | Nausea, vomiting, diarrhoea, constipation [Source: NHS tirzepatide page] |
| GI severity | Mostly mild-to-moderate; highest at dose increases | Mostly mild-to-moderate; typically settles within ~2 weeks [Source: SURMOUNT-1, NEJM] |
| Pancreatitis signal | Observed at low frequency in phase 2 | Known class risk; MHRA Drug Safety Update, January 2026 |
| Evidence depth | Phase 2 only; phase 3 pending | Full phase 3 programme; MHRA-licensed; post-marketing surveillance ongoing |
| UK licensing status | Not licensed; not available | Licensed for weight management (BMI ≥30, or ≥27 with a weight-related condition) |
Because retatrutide has not completed phase 3 trials, any claim about its side-effect profile relative to tirzepatide at scale would be speculative. The five most frequently reported Mounjaro side effects are well-documented; an equivalent list for retatrutide does not yet exist with the same confidence.
What this means for anyone considering treatment today
Retatrutide is not available from any UK pharmacy, including ours. Any website claiming to sell it in the UK is not offering a licensed product. The only triple-agonist weight-loss treatment you will see discussed in UK clinical settings right now is tirzepatide's licensing context, and even that term is sometimes confused with retatrutide in online searches. If you have read about retatrutide and are wondering whether it might suit you better than tirzepatide, the honest answer is that there is not enough safety data to say either way, and it is not an option. Tirzepatide, on the other hand, has an established tolerability record, a UK licence, and an MHRA-monitored supply chain. The question of whether you might tolerate Mounjaro without significant side effects is worth exploring before ruling it out. Some people also ask about what to do if side effects do appear, that page covers practical management steps. Our free consultation is the right place to go through your individual history, current medicines and any concerns; a GPhC-registered prescriber will review your answers the same day. Which medicine suits you is a clinical decision our prescribers make with you.
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