Retatrutide: what it is, what the trials show and where it stands in the UK
Eli Lilly's retatrutide is the first 'triple agonist' to reach late-stage trials. Here is what the published research says, trial by trial, and why it is not a licensed medicine in the UK.
By the RetaRadar team · Updated 30 September 2026
In short: retatrutide (development code LY3437943) is an investigational once-weekly injection from Eli Lilly that activates three hormone receptors — GIP, GLP-1 and glucagon. In a phase 2 obesity trial, people in the highest dose arm lost an average of 24.2% of their body weight over 48 weeks. Phase 3 trials reported in 2025–2026 have shown average losses of up to 28.7%. It has not been approved anywhere, and the MHRA has not authorised it in the UK.
This page is a summary of published research for general information. It does not give, and should not be read as, advice on using retatrutide. Figures come from the papers and company announcements linked in the text.
What retatrutide is
Retatrutide is a single peptide of 39 amino acids, built on a GIP backbone and modified so it lasts long enough in the body for weekly dosing. Lilly's discovery paper in Cell Metabolism describes it as an agonist at three receptors: glucagon (GCGR), glucose-dependent insulinotropic polypeptide (GIPR) and glucagon-like peptide-1 (GLP-1R). In laboratory tests its activity at the glucagon and GLP-1 receptors was balanced and its activity at the GIP receptor was higher (Coskun et al., 2022).
How a triple agonist differs from Wegovy and Mounjaro
The licensed weight-management medicines in the UK work through one or two of these receptors:
- Semaglutide (Wegovy) activates the GLP-1 receptor, which slows stomach emptying and reduces appetite.
- Tirzepatide (Mounjaro) activates both the GIP and GLP-1 receptors.
- Retatrutide adds the glucagon receptor. In animal studies, glucagon-receptor activity increased energy expenditure on top of the reduced food intake driven by GIP and GLP-1 (Coskun et al., 2022).
Glucagon normally raises blood sugar, so combining it with GLP-1 and GIP activity, which lower blood sugar, is a balancing act. That is one reason the trials track heart rate, blood glucose and liver fat closely.
Early trials: phase 1 and phase 1b
The first human study, a single-dose trial in healthy volunteers, is reported in the same Cell Metabolism paper. Weight reduction after one dose lasted up to day 43.
A 12-week phase 1b trial in 72 people with type 2 diabetes, published in The Lancet, found a half-life of about six days. In the higher-dose groups, HbA1c (a measure of long-term blood sugar) fell by up to 1.6 percentage points and body weight by up to 8.96 kg compared with placebo. Adverse events were reported by 63% of people on retatrutide and 54% on placebo, mostly gastrointestinal (Urva et al., 2022).
Phase 2: the results that drew attention
Obesity (NEJM, 2023)
The phase 2 obesity trial randomised 338 adults with a BMI of 30 or more, or 27 or more with a weight-related condition, to retatrutide or placebo for 48 weeks (Jastreboff et al., New England Journal of Medicine, 2023).
| Measure | Highest dose arm | Placebo |
|---|---|---|
| Average weight change at 24 weeks | −17.5% | −1.6% |
| Average weight change at 48 weeks | −24.2% | −2.1% |
| Lost at least 10% of body weight by 48 weeks | 93% | 9% |
| Lost at least 15% of body weight by 48 weeks | 83% | 2% |
The most common side effects were gastrointestinal and dose-related, mostly mild to moderate. Heart rate rose with dose, peaked at 24 weeks and then declined.
Type 2 diabetes (The Lancet, 2023)
In 281 people with type 2 diabetes, HbA1c fell by 2.02 percentage points at 24 weeks in the highest dose arm, against 0.01 on placebo and 1.41 on dulaglutide, an established GLP-1 medicine. Body weight fell by 16.94% at 36 weeks in the highest dose arm, against 3.00% on placebo (Rosenstock et al., 2023).
Liver fat (Nature Medicine, 2024)
A sub-study of 98 participants with metabolic dysfunction-associated steatotic liver disease (MASLD) found liver fat fell by 82.4% at 24 weeks in the highest dose arm, against a 0.3% rise on placebo. 86% of that arm reached normal liver fat levels, against none on placebo (Sanyal et al., 2024).
Phase 3: the TRIUMPH and TRANSCEND programmes
Lilly's phase 3 programme covers obesity (TRIUMPH) and type 2 diabetes (TRANSCEND-T2D). Five trials had reported results by the end of September 2026. Unless stated, figures are from Lilly's announcements and use the "efficacy estimand", which assumes people stayed on treatment. It gives larger effects than an analysis that counts everyone who started.
| Trial | Participants | Result, highest dose arm vs placebo |
|---|---|---|
| TRIUMPH-4 (knee osteoarthritis), 68 weeks | 445 | Weight −28.7% vs −2.1%; knee pain score (WOMAC) −75.8% vs −40.3% (Lilly, 11 December 2025) |
| TRANSCEND-T2D-1 (type 2 diabetes), 40 weeks | 537 | HbA1c −1.7 to −2.0 points across doses vs −0.8; weight −16.8% vs −2.5% (Lilly, 19 March 2026; later published in The Lancet) |
| TRIUMPH-1 (obesity), 80 weeks | 2,339 | Weight −28.3% vs −2.2%; 45.3% lost at least 30% of body weight vs 0.5% (Lilly, 21 May 2026) |
| TRIUMPH-2 (obesity with type 2 diabetes), 80 weeks | 1,152 | Weight −20.8% vs −4.0%; HbA1c −1.4 to −1.6 points vs −0.2 |
| TRIUMPH-3 (obesity with cardiovascular disease), 80 weeks | 1,949 | Weight −22.6% vs −3.2% (TRIUMPH-2 and -3: Lilly, 23 July 2026) |
Full TRIUMPH-2 results were presented at the EASD meeting in Milan and published in The Lancet on 29 September 2026, according to Lilly's announcement.
The full phase 3 programme
| Trial | ClinicalTrials.gov | Population | Status (September 2026) |
|---|---|---|---|
| TRIUMPH-1 | NCT05929066 | Obesity or overweight without type 2 diabetes (with knee osteoarthritis and sleep apnoea sub-studies) | Completed; topline 21 May 2026 |
| TRIUMPH-2 | NCT05929079 | Obesity or overweight with type 2 diabetes | Completed; full results 29 September 2026 |
| TRIUMPH-3 | NCT05882045 | Severe obesity with established cardiovascular disease | Completed; topline 23 July 2026 |
| TRIUMPH-4 | NCT05931367 | Obesity or overweight with knee osteoarthritis | Completed; topline 11 December 2025 |
| TRIUMPH-5 | NCT06662383 | Head-to-head against tirzepatide | Ongoing |
| TRIUMPH-6 to -9 | NCT06859268, NCT07035093, NCT07232719, NCT07357415 | Weight maintenance, chronic low back pain and further obesity populations | Ongoing |
| TRIUMPH-Outcomes | NCT06383390 | Cardiovascular and kidney outcomes, about 10,000 participants | Ongoing (to 2029) |
| TRANSCEND-T2D-1 | NCT06354660 | Type 2 diabetes managed with diet and exercise, against placebo | Completed; topline 19 March 2026 |
| TRANSCEND-T2D-2 | NCT06260722 | Type 2 diabetes, against semaglutide | Ongoing |
| TRANSCEND-T2D-3 | NCT06297603 | Type 2 diabetes with kidney impairment | Ongoing |
The trial that matters most for regulators in the long run is TRIUMPH-Outcomes, which tests whether retatrutide reduces heart attacks, strokes and kidney disease. It is not expected to finish before 2029.
Side effects reported so far
As with other drugs in this class, gastrointestinal effects are the most common. In TRIUMPH-1, in the highest dose arm against placebo:
- nausea: 42.4% vs 14.8%
- diarrhoea: 32.0% vs 13.5%
- vomiting: 25.3% vs 4.8%
- stopping treatment because of side effects: 11.3% vs 4.9%
The phase 3 trials also reported dysaesthesia, an abnormal or unpleasant skin sensation, which is not typical of GLP-1 medicines. It affected 20.9% of the highest dose arm in TRIUMPH-4 (against 0.7% on placebo) and 12.5% in TRIUMPH-1 (against 0.9%). In TRIUMPH-4, 18.2% of the highest dose arm stopped treatment because of side effects, against 4.0% on placebo. Regulators will weigh these findings when Lilly applies for approval.
Regulatory status
In the UK
Retatrutide is not authorised by the Medicines and Healthcare products Regulatory Agency (MHRA). Outside a clinical trial it cannot legally be supplied as a medicine. In July 2026 the MHRA warned that "it has not been authorised for use in the UK, meaning anyone selling this product is doing so illegally" (MHRA, 24 July 2026).
The MHRA has also carried out raids on illegal production. In October 2025 it seized more than 2,000 unlicensed retatrutide and tirzepatide pens from what it called the first illicit weight-loss medicine production facility found in the UK (MHRA, October 2025). In May 2026 it made its largest seizure of unlicensed weight-loss medicines to date, about 12,000 doses including retatrutide, and two people were arrested (MHRA, May 2026).
Elsewhere
No regulator has approved retatrutide. In July 2026 Lilly said it plans to submit a Biologics License Application to the US Food and Drug Administration in the first quarter of 2027. Lilly has not announced a date for applications to the European Medicines Agency or the MHRA.
Research-grade retatrutide in the UK
Retatrutide is also sold online as a "research chemical", labelled for laboratory use only and not for human consumption. These products are not medicines: they are not made to pharmaceutical standards, not checked by the MHRA and not the product used in Lilly's trials. Quality varies. That is why our supplier ratings focus on independent lab reports, identifiable companies and whether a shop gives human-use advice. It is also why every rating page carries the MHRA warning.
Our sponsored partner LeoLab lists research-grade retatrutide on LeoLab's retatrutide page; see our LeoLab review for how it scores. If you are looking for weight-loss treatment, licensed options are available through the NHS and registered pharmacies — see Mounjaro and Wegovy on the NHS.
Sources
- Coskun T, et al. LY3437943, a novel triple GIP, GLP-1 and glucagon receptor agonist. Cell Metabolism, 2022. PMID 35985340
- Urva S, et al. Phase 1b trial in type 2 diabetes. The Lancet, 2022. PMID 36354040
- Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity. NEJM, 2023. PMID 37366315
- Rosenstock J, et al. Retatrutide in type 2 diabetes, phase 2. The Lancet, 2023. PMID 37385280
- Sanyal AJ, et al. Retatrutide and liver fat in MASLD. Nature Medicine, 2024. PMID 38858523
- ClinicalTrials.gov records for the NCT numbers listed above, retrieved 30 September 2026. Search
- MHRA press releases, October 2025, May 2026 and July 2026, linked in the text.