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Retatrutide (development code LY3437943, often shortened to “Reta”) is an investigational peptide developed by Eli Lilly. It is described as a triple agonist because it acts on three receptors at once: the GIP receptor, the GLP-1 receptor and the glucagon receptor. That combination is what sets it apart from semaglutide (GLP-1 only) and tirzepatide (GIP and GLP-1). This guide explains what retatrutide is, what the published trials have reported, the side effects recorded in those trials, the doses that were studied, and the current regulatory position in the UK.
What is retatrutide?
Retatrutide is a single synthetic peptide engineered from the glucagon backbone, with modifications that give it activity at all three receptors and a half-life long enough for once-weekly dosing in trials. Its GLP-1 activity is associated with reduced appetite and slower gastric emptying; GIP activity has been linked with improved insulin response and possibly reduced nausea; and glucagon-receptor activity is thought to increase energy expenditure and hepatic fat clearance. The interest in a triple agonist is that these mechanisms may be additive.
It is important to be clear about status: as of the date of this article retatrutide is not a licensed medicine in the UK, the EU or the US. It remains in late-stage clinical development. Any “retatrutide” sold in the UK is therefore either a research-use-only reference material or an unlicensed product; it is not the pharmaceutical product being tested in Lilly’s trials.
Retatrutide and weight loss: what the trials reported
The headline data come from a Phase 2 trial published in the New England Journal of Medicine in 2023 (Jastreboff et al.). Adults with obesity or overweight, without diabetes, were randomised to placebo or to once-weekly retatrutide at 1 mg, 4 mg, 8 mg or 12 mg for 48 weeks.
- At 24 weeks, mean weight reduction ranged from about 7.2% (1 mg) to 17.5% (12 mg), versus 1.6% on placebo.
- At 48 weeks, mean weight reduction reached approximately 8.7% (1 mg), 17.3% (4 mg), 22.8% (8 mg) and 24.2% (12 mg), versus 2.1% on placebo.
- Weight had not clearly plateaued at 48 weeks in the higher-dose groups.
A separate Phase 2 study in adults with type 2 diabetes (published in The Lancet, 2023) reported dose-dependent reductions in HbA1c and body weight across doses from 0.5 mg to 12 mg weekly. A Phase 3 programme (TRIUMPH) covering obesity, obesity with cardiovascular disease, knee osteoarthritis and obstructive sleep apnoea is under way; results from those studies, not the Phase 2 data, will determine whether and how retatrutide is licensed.
These are population averages from supervised trials with structured dose escalation and lifestyle support. They do not describe what happens to any individual, and they say nothing about unlicensed material of unknown identity and purity.
Retatrutide side effects recorded in trials
The adverse-event profile in the Phase 2 trials was broadly similar to other incretin-based therapies, with some differences attributed to the glucagon component:
- Gastrointestinal effects were the most common: nausea, diarrhoea, vomiting and constipation. They were dose-related, mostly mild to moderate, and occurred mainly during dose escalation. Discontinuation because of side effects was more frequent at higher doses (roughly 6–16% across the active arms in the obesity study).
- Heart rate increased by a few beats per minute on average, peaking around week 24 and declining thereafter.
- Skin sensitivity / dysaesthesia (unusual skin sensations) was reported in a small proportion of participants at higher doses, an effect not typically seen with GLP-1-only drugs.
- Cardiac arrhythmia signals were reported in a small number of participants and are being examined further in Phase 3.
Because retatrutide is unlicensed, there is no summary of product characteristics, no established contraindication list and no post-marketing safety data. The class warnings that apply to GLP-1 medicines (pancreatitis, gallbladder disease, thyroid C-cell tumours in rodents, and the risks of use during pregnancy) are relevant context but have not been formally characterised for retatrutide.
What doses have been used in published research?
For context only: the obesity Phase 2 trial used once-weekly subcutaneous doses of 1 mg, 4 mg, 8 mg and 12 mg, reached through stepped escalation from starting doses of 1 mg or 2 mg over the first 4–12 weeks. The type 2 diabetes study additionally included 0.5 mg and 1.5 mg arms. Escalation schedules were part of the protocol specifically to manage gastrointestinal side effects. No dose has been approved by any regulator, and this article does not provide a dosing schedule.
Is retatrutide legal in the UK?
Retatrutide is not a controlled drug under the Misuse of Drugs Act, but it is also not an authorised medicine. In the UK, supplying a product for human use with claims to treat obesity or diabetes would bring it within the MHRA’s medicines framework and, without a marketing authorisation, would be unlawful. Research-use-only reference material can be supplied to laboratories and researchers provided it is not marketed or supplied for human consumption. That distinction is why reputable UK suppliers label retatrutide “for research use only” and do not provide usage instructions. Regulatory requirements depend on the jurisdiction and circumstances; this is not legal advice.
Retatrutide vs tirzepatide vs semaglutide
| Compound | Receptor targets | UK status | Reported mean weight change (trial, duration) |
|---|---|---|---|
| Semaglutide 2.4 mg | GLP-1 | Licensed (Wegovy) | ~14.9% (STEP 1, 68 weeks) |
| Tirzepatide 15 mg | GIP + GLP-1 | Licensed (Mounjaro) | ~20.9% (SURMOUNT-1, 72 weeks) |
| Retatrutide 12 mg | GIP + GLP-1 + glucagon | Investigational | ~24.2% (Phase 2, 48 weeks) |
Cross-trial comparisons are indicative only: populations, durations and endpoints differ, and Phase 2 results frequently shrink in larger Phase 3 studies.
Retatrutide as a research material
Laboratories working with retatrutide as a reference standard should look for the same things as with any peptide: a batch-specific certificate of analysis showing HPLC purity and mass spectrometry confirming the expected molecular weight, lyophilised format, and cold-chain storage. Our Retatrutide 10mg listing is supplied for research use only with batch documentation. See also what HPLC purity and a COA actually mean.
Retatrutide frequently asked questions
Is retatrutide available in the UK?
Not as a medicine. It has no UK marketing authorisation and cannot be prescribed. Research-use reference material is available to laboratories and researchers.
What does “reta” mean?
“Reta” is simply the informal shorthand for retatrutide used online. It refers to the same compound, LY3437943.
How is retatrutide different from Mounjaro?
Mounjaro (tirzepatide) acts on two receptors, GIP and GLP-1. Retatrutide adds a third, the glucagon receptor, which is believed to contribute to higher energy expenditure.
When will retatrutide be approved?
That depends on the Phase 3 TRIUMPH results and regulatory review. No approval date has been announced by the MHRA, EMA or FDA at the time of writing.
Are the side effects of retatrutide worse than semaglutide?
The trials reported the same broad pattern of gastrointestinal effects. Additional signals unique to retatrutide included skin sensitivity and a somewhat larger heart-rate rise. Direct head-to-head safety data do not yet exist.
How should you interpret the evidence?
Retatrutide’s Phase 2 results are among the largest weight reductions reported for any pharmacological agent, which explains the search interest. They are still Phase 2 results. Until Phase 3 data are published and a regulator has reviewed them, statements about efficacy and safety should be read as provisional, and any product sold outside a trial is not the product that was studied.
Sources: Jastreboff AM et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med 2023;389:514-526. Rosenstock J et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 2023;402:529-544.