Retatrutide Trial Results: Phase 2 to the TRIUMPH Phase 3 Readouts

LynxLab · 24 October 2026 · 9 min read

What the 2023 phase 2 trial and the TRIUMPH phase 3 programme found for retatrutide: weight change by dose, side effects, and what was reported by October 2026.

Photo: Samuel Ramos, Unsplash

Retatrutide is Eli Lilly's once-weekly injectable peptide that acts on three hormone receptors at once: GIP, GLP-1 and glucagon. Between June 2023 and October 2026 it went from a single phase 2 paper in the New England Journal of Medicine to five completed phase 3 trials, two of them now published in full.

The figures have drawn attention because they are larger than anything reported for a licensed obesity drug. They also come with caveats about how the numbers were calculated, who was enrolled, and what has not yet been published. The sections below take each trial in order, with the results as the journals and Lilly stated them. The product page for retatrutide covers what the molecule is; this post covers the evidence.

What the 2023 phase 2 trial found

The phase 2 trial was led by Ania Jastreboff of Yale School of Medicine and published in the New England Journal of Medicine on 26 June 2023. It enrolled 338 adults with a BMI of 30 or above, or 27 or above with a weight-related condition, and ran for 48 weeks at sites in the United States.

Participants were randomised to weekly doses of 1mg, 4mg, 8mg or 12mg of retatrutide, or placebo. Two of the arms began at 2mg to test whether a gentler start reduced stomach side effects.

At 48 weeks the mean weight change was 8.7% in the 1mg group, 17.1% in the combined 4mg groups, 22.8% in the combined 8mg groups and 24.2% in the 12mg group, against 2.1% with placebo (Jastreboff et al., NEJM 2023). Every participant on 8mg or 12mg lost at least 5% of their body weight.

The paper also recorded dose-dependent increases in heart rate that peaked at 24 weeks and then declined, and noted that gastrointestinal events were partly reduced by the 2mg starting dose. Both observations shaped the phase 3 design. Anyone comparing research-grade retatrutide with the trial compound should note that the phase 2 molecule was Lilly's own LY3437943, given under medical supervision.

How the TRIUMPH phase 3 programme was built

Lilly named the phase 3 programme TRIUMPH and started it in 2023. The four registration trials enrolled more than 5,800 participants and tested three target doses, 4mg, 9mg and 12mg weekly, each reached by stepping up from 2mg every four weeks (Lilly, May 2026).

The trials were built as master and basket studies. TRIUMPH-1 was the main obesity trial and contained two baskets, one for knee osteoarthritis pain and one for obstructive sleep apnoea. TRIUMPH-2 did the same for people with type 2 diabetes. TRIUMPH-3 enrolled people with severe obesity and established cardiovascular disease, and TRIUMPH-4 was a separate knee osteoarthritis trial.

Two statistical readings matter when reading any of the results. The efficacy estimand counts people who stayed on treatment. The treatment-regimen estimand counts everyone randomised, whether or not they stopped, and it is always the smaller number. Lilly's press releases lead with the first; the journals lead with the second.

TRIUMPH-4 came first, in December 2025

Lilly announced TRIUMPH-4 topline results on 11 December 2025. The trial randomised 445 adults with obesity or overweight and knee osteoarthritis, without diabetes, to 9mg, 12mg or placebo for 68 weeks (Lilly, December 2025).

Weight fell by an average of 26.4% on 9mg and 28.7% on 12mg, against 2.1% on placebo, using the efficacy estimand. On the treatment-regimen estimand the figures were 20.0%, 23.7% and 4.6%.

The co-primary pain endpoint used the WOMAC pain scale. Scores fell by 4.5 points (75.8%) on 9mg and 4.4 points (74.3%) on 12mg from a baseline of 6.0, against 2.4 points on placebo. In a post-hoc analysis, 14.1% and 12.0% of participants on the two doses reported no knee pain at all at 68 weeks, compared with 4.2% on placebo.

Each readout has been followed by a rise in people trying to buy retatrutide outside a trial, which is why the UK regulator has issued repeated statements. That side of the story is covered in retatrutide's UK status and the MHRA position.

TRIUMPH-1 reported in May and September 2026

TRIUMPH-1 randomised 2,339 adults with obesity or overweight, at least one weight-related condition and no diabetes to 4mg, 9mg, 12mg or placebo for 80 weeks. Lilly released topline figures on 21 May 2026, and the full paper, again led by Jastreboff, appeared in the New England Journal of Medicine on 29 September 2026.

On the efficacy estimand, average weight loss at 80 weeks was 19.0% on 4mg, 25.9% on 9mg and 28.3% on 12mg, against 2.2% on placebo, from a mean baseline of 112.7kg (Lilly, May 2026). The published intention-to-treat figures were 17.6%, 23.7% and 25.0% against 3.9% (Jastreboff et al., NEJM 2026).

Lilly also reported that 65.3% of participants on 12mg finished with a BMI below 30, and that 45.3% lost 30% or more of their body weight. A pre-specified extension took 532 participants with a baseline BMI of 35 or above out to 104 weeks, where those on 12mg had lost an average of 30.3%.

The basket results were published in the same NEJM paper. Among the 574 participants with knee osteoarthritis, pain scores fell by 3.5 and 3.6 points on 9mg and 12mg against 1.9 on placebo. Among the 243 with obstructive sleep apnoea, the apnoea-hypopnoea index fell by 34.3 and 31.7 events per hour against 9.9 on placebo.

LynxLab stocks retatrutide in the UK for research use in 10mg (£59.99), 20mg (£99.99) and 30mg (£134.99) vials, tested to 99% purity, with the lab report for each batch on the product page.

TRIUMPH-2 and TRIUMPH-3 covered diabetes and heart disease

Lilly released TRIUMPH-2 and TRIUMPH-3 topline results together on 23 July 2026. In the same statement it said it planned to file a Biologics License Application with the US FDA in the first quarter of 2027 (Lilly, July 2026).

TRIUMPH-2 enrolled 1,152 adults with type 2 diabetes and a BMI of 27 or above. The full paper, led by Virginia Bellido of Virgen del Rocío University Hospital in Seville, was published in The Lancet on 29 September 2026. On the treatment-regimen estimand, weight fell by 11.9% on 4mg, 16.8% on 9mg and 18.8% on 12mg at 80 weeks, against 5.1% on placebo (Bellido et al., The Lancet 2026). HbA1c fell by up to 1.6 percentage points from a baseline of 7.7%.

TRIUMPH-3 randomised 1,949 adults with a BMI of 35 or above and established cardiovascular disease to 9mg, 12mg or placebo. Weight fell by up to 22.6% at 80 weeks. In a pre-specified analysis there were 44 major cardiovascular events (MACE-5) on retatrutide and 52 on placebo, a hazard ratio of 0.82 with a confidence interval of 0.55 to 1.22 (Lilly, July 2026).

The trial was not powered to prove a cardiovascular benefit, and the narrower MACE-3 measure went the other way, with 27 events against 23 and a hazard ratio of 1.12. A dedicated outcomes trial is still running. Laboratories ordering retatrutide vials for receptor or metabolic work will find the TRIUMPH-3 lipid data more useful: triglycerides fell 37.0% and hsCRP 51.2% on the top dose.

What the side effect data show

Across every trial the most common adverse events were gastrointestinal: nausea, diarrhoea, constipation, vomiting and reduced appetite. In TRIUMPH-4, nausea affected 38.1% of the 9mg group and 43.2% of the 12mg group against 10.7% on placebo (Lilly, December 2025).

Two less familiar signals recur. Dysesthesia, an altered skin sensation such as tingling or heightened sensitivity to touch, affected 8.8% and 20.9% of the TRIUMPH-4 dose groups against 0.7% on placebo, and 4% to 7% of participants in TRIUMPH-2. Hypotension was also more frequent than placebo in TRIUMPH-2 (Bellido et al., The Lancet 2026).

Discontinuation because of adverse events ranged from 3.8% on 4mg in TRIUMPH-2 to 18.2% on 12mg in TRIUMPH-4. Lilly said the TRIUMPH-4 figure included people who stopped because they felt they had lost too much weight, and that the rate was lower among those with a baseline BMI of 35 or above.

Deaths were rare and investigators judged none related to treatment. In TRIUMPH-2 there were two deaths in the 4mg group, three in the 9mg group, one in the 12mg group and one on placebo.

What has not been reported yet

As of 24 October 2026, TRIUMPH-3 and TRIUMPH-4 exist only as press releases; the peer-reviewed papers have not appeared. The 104-week extension figures from TRIUMPH-1 also came from Lilly rather than a journal, and Lilly's headline numbers use the more favourable estimand.

Several trials are still running. Lilly's own list includes phase 3 studies in chronic low back pain, cardiovascular and renal outcomes, and metabolic dysfunction-associated steatotic liver disease (Lilly, July 2026). None had reported by October 2026.

No regulator has approved retatrutide for any use. How the figures above sit next to the two licensed incretin drugs is set out in retatrutide vs tirzepatide vs semaglutide. Batch lab reports for every LynxLab product are published on the quality page, and the retatrutide for research page carries the report for the current batch.

Frequently asked questions

How much weight did people lose on retatrutide in trials?

In the phase 2 trial, the 12mg group lost an average of 24.2% of body weight at 48 weeks (Jastreboff et al., NEJM 2023). In TRIUMPH-1, the 12mg group lost 28.3% at 80 weeks on the efficacy estimand and 25.0% on the intention-to-treat analysis (NEJM 2026). People with type 2 diabetes in TRIUMPH-2 lost less, 18.8% on the intention-to-treat analysis.

Has retatrutide finished phase 3 trials?

The four registration trials for obesity, knee osteoarthritis and sleep apnoea have all reported topline results, the last two on 23 July 2026. Lilly said it planned to file with the US FDA in the first quarter of 2027. Trials in liver disease, back pain and cardiovascular outcomes are still running.

What were the side effects of retatrutide in the trials?

Nausea, diarrhoea, constipation and vomiting were the most common, as with other GLP-1 drugs. Dysesthesia (tingling or altered skin sensation) and low blood pressure were more frequent than placebo, and the phase 2 trial recorded a rise in heart rate that peaked at 24 weeks. Between 4% and 18% of participants stopped because of side effects, depending on dose and trial.

Is retatrutide approved anywhere?

No. As of October 2026 retatrutide has no marketing authorisation in any country. The MHRA has stated that it is not authorised for use in the UK, and Lilly's FDA filing was scheduled for early 2027.

Sources

Research use only

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