Eli Lilly reported topline results from TRIUMPH-2 and TRIUMPH-3 on 23 July 2026. Both are pivotal, randomised, double-blind, placebo-controlled Phase 3 trials of retatrutide (LY3437943), an investigational once-weekly peptide that agonises the receptors for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon. In both studies the sponsor-defined primary endpoint of percent change in body weight at 80 weeks was met at the doses tested for that claim.[1]

These figures are company-disclosed. They have not yet been presented at a medical meeting or published in a peer-reviewed journal. They should be read as topline, efficacy-estimand results, not as licensed-indication data. Retatrutide is not authorised by the MHRA. It is not a UK licensed medicine, and nothing in this article is consumption, dosing or self-administration advice.

1. What was reported

TRIUMPH-2 enrolled adults with type 2 diabetes and obesity or overweight. TRIUMPH-3 enrolled adults with severe obesity (BMI ≥35 kg/m²) and established cardiovascular disease, with or without type 2 diabetes. Together they extend the Phase 3 dataset beyond the earlier TRIUMPH-1 obesity readout and the TRIUMPH-4 knee-osteoarthritis readout already covered on this site.[1][4][5]

Lilly stated that, across five positive Phase 3 studies, it now considers the clinical package sufficient to support global submissions for obesity, knee osteoarthritis pain and obstructive sleep apnoea, and that it plans a Biologics License Application to the US Food and Drug Administration in the first quarter of 2027 after completing the chemistry, manufacturing and controls (CMC) package.[1] That is a US-jurisdiction filing intention. It is not an MHRA decision, not a UK licence, and not a NICE appraisal.

The sponsor also stated that retatrutide “cannot be legally sold or marketed for human use” while it remains investigational.[1]

2. TRIUMPH-2: obesity or overweight with type 2 diabetes

TRIUMPH-2 (NCT05929079) is an 80-week Phase 3 trial under a basket design. It randomised 1,152 participants 1:1:1:1 to retatrutide 4 mg, 9 mg or 12 mg, or placebo, given once weekly. Participants assigned to retatrutide started at 2 mg and increased every four weeks to the assigned target. A four-week post-treatment follow-up was included.[1][2]

Registry eligibility required BMI ≥27.0 kg/m², type 2 diabetes on stable treatment for at least 90 days, and at least one unsuccessful dietary weight-loss attempt. Type 1 diabetes, recent substantial weight change, recent use of weight-loss drugs, prior or planned obesity surgery, a personal or family history of medullary thyroid carcinoma or MEN-2, and prior pancreatitis were among the exclusions. A nested obstructive-sleep-apnoea protocol (GSA2) is registered; those apnoea endpoints were not included in this topline.[2]

Mean baseline body weight was 106.4 kg (BMI 38.2 kg/m²). Mean baseline HbA1c was 7.7%.[1]

Under the efficacy estimand at week 80, mean percent change in body weight was:

  • retatrutide 4 mg: −12.7% (−13.5 kg)
  • retatrutide 9 mg: −19.1% (−20.6 kg)
  • retatrutide 12 mg: −20.8% (−22.5 kg)
  • placebo: −4.0% (−4.2 kg)

The 4 mg weight-change result was designated a key secondary endpoint rather than a primary endpoint.[1]

Mean change in HbA1c from the 7.7% baseline was −1.4, −1.6 and −1.5 percentage points at 4 mg, 9 mg and 12 mg respectively, versus −0.2 percentage points with placebo.[1]

The 20.8% mean reduction at 12 mg is lower than the 28.3% reported at the same dose and time point in TRIUMPH-1, which enrolled adults with obesity or overweight without diabetes.[5] That pattern is consistent with the incretin literature: percent weight loss in type 2 diabetes is typically smaller than in non-diabetic obesity cohorts. It does not, on its own, establish a comparison with tirzepatide or semaglutide, because TRIUMPH-2 was placebo-controlled, not an active-comparator trial.

3. TRIUMPH-3: severe obesity with established cardiovascular disease

TRIUMPH-3 (NCT05882045) is an 80-week Phase 3 trial that randomised 1,949 participants 1:1:2 to retatrutide 9 mg, retatrutide 12 mg, or placebo. Titration again began at 2 mg once weekly, increasing every four weeks to the assigned target.[1][3]

Inclusion required BMI ≥35 kg/m² and established cardiovascular disease, defined as prior myocardial infarction, prior ischaemic or haemorrhagic stroke, or symptomatic peripheral arterial disease, plus at least one unsuccessful dietary weight-loss attempt. Recent acute coronary or heart-failure events, recent weight-loss drugs, prior or planned obesity surgery, type 1 diabetes, MTC/MEN-2 history and prior pancreatitis were among the exclusions.[3]

Mean baseline body weight was 111.4 kg (BMI 40.4 kg/m²).[1]

Under the efficacy estimand at week 80, mean percent change in body weight was:

  • retatrutide 9 mg: −21.6% (−23.9 kg)
  • retatrutide 12 mg: −22.6% (−25.3 kg)
  • placebo: −3.2% (−3.5 kg)

At 12 mg the sponsor also reported mean reductions of 37.0% in triglycerides, 16.5% in non-HDL cholesterol, 9.3 mmHg in systolic blood pressure, 19.0 cm in waist circumference, and 51.2% in high-sensitivity C-reactive protein (hsCRP).[1] These are associated biomarker changes in a high-risk cohort. They are not a demonstration that retatrutide prevents myocardial infarction, stroke or cardiovascular death.

4. Cardiovascular events in TRIUMPH-3 are inconclusive

TRIUMPH-3 was not a dedicated cardiovascular outcomes trial. Event counts were low, and both pre-specified confidence intervals crossed 1.

For time to first MACE-5 (all-cause death, myocardial infarction, stroke, heart-failure event, or coronary revascularisation), the in-study analysis recorded 44 events in participants randomised to pooled retatrutide 9 mg and 12 mg and 52 events with placebo, giving a hazard ratio of 0.82 (95% CI 0.55 to 1.22). For MACE-3 (cardiovascular death, myocardial infarction or stroke) there were 27 events with retatrutide and 23 with placebo, hazard ratio 1.12 (95% CI 0.64 to 1.96).[1]

A non-pre-specified on-treatment analysis, which excluded events more than 35 days after stopping assigned treatment, produced hazard ratios of 0.73 (0.47 to 1.12) for MACE-5 and 0.92 (0.51 to 1.65) for MACE-3.[1] Those intervals also cross 1.

The correct reading is that TRIUMPH-3 does not establish cardiovascular benefit or harm. A dedicated outcomes study would be required to answer that question. Lilly lists cardiovascular and renal outcomes among the indications under Phase 3 evaluation; this topline does not report that programme.[1]

5. Safety and discontinuations

Gastrointestinal events predominated, as in earlier incretin-class trials.

In TRIUMPH-2 the most common adverse events with retatrutide 4 mg, 9 mg and 12 mg versus placebo were diarrhoea (27.4%, 33.5%, 33.6% vs 13.2%), nausea (13.7%, 20.8%, 28.0% vs 8.0%), constipation (14.0%, 16.2%, 16.8% vs 9.4%), decreased appetite (5.8%, 12.3%, 17.1% vs 4.5%) and vomiting (5.5%, 10.2%, 15.7% vs 4.2%). Dysesthesia occurred in 4.5%, 5.6% and 7.3% versus 0.7% with placebo; urinary-tract infection in 3.8%, 6.3% and 8.0% versus 6.6%. Discontinuation because of adverse events was 3.8% (4 mg), 11.6% (9 mg) and 7.7% (12 mg) versus 4.9% with placebo.[1]

In TRIUMPH-3 the most common events at 9 mg and 12 mg versus placebo were diarrhoea (30.1%, 24.4% vs 8.7%), nausea (21.7%, 22.4% vs 5.8%), constipation (18.0%, 15.7% vs 7.1%) and decreased appetite (13.5%, 14.5% vs 3.0%). Hyperglycaemia was reported less often on retatrutide (3.9%, 3.1%) than on placebo (13.4%). Dysesthesia occurred in 6.4% at both retatrutide doses versus 1.3% with placebo; urinary-tract infection in 6.1% and 7.0% versus 5.3%. Discontinuation because of adverse events was 9.8% (9 mg) and 13.5% (12 mg) versus 4.8% with placebo.[1]

Lilly described dysesthesia and urinary-tract infection events as generally mild to moderate, with the majority resolving during treatment.[1] That characterisation is the sponsor’s. Full adverse-event tables, including serious events, pancreatitis, gallbladder disease, retinopathy and heart-rate change, are not in this topline.

The 9 mg arm in TRIUMPH-2 had a higher adverse-event discontinuation rate (11.6%) than the 12 mg arm (7.7%). That inversion is unexplained in the press release and should not be over-interpreted until the full dataset is public.

6. How to read the estimand

Reported efficacy uses the efficacy estimand: the effect had all randomised participants remained on study intervention (with possible dose interruptions and modifications) without starting prohibited weight-management treatments, and without glycaemic rescue for glycaemic endpoints.[1] That is not the same as a treatment-regimen (intention-to-treat) estimand, which includes people who stopped the drug. Treatment-regimen figures were not disclosed in this topline. In incretin obesity trials the two estimands often diverge, particularly where gastrointestinal discontinuation is material. Until both are published, the 20.8% and 22.6% figures should not be treated as the expected mean change in a population that includes non-adherence.

7. UK regulatory position

Retatrutide is not licensed by the MHRA for any indication. It does not appear on the UK register of licensed medicines. Under the Human Medicines Regulations 2012, a medicinal product may not be placed on the UK market without a marketing authorisation except in defined exemptions. The Medicines Act 1968 remains the parent statute. A US BLA filing, even if submitted in 2027 and subsequently granted, would not itself create a UK licence; the MHRA would require a separate marketing-authorisation application. Any subsequent NHS use would then depend on NICE appraisal. None of those steps has occurred.[1][6]

If a UK licence were ever granted, retatrutide would be expected to be a prescription-only medicine (POM), in line with licensed GLP-1 and dual GIP/GLP-1 receptor agonists already on the UK market. That is a prediction about legal classification, not a statement that the compound is available.

Unlicensed peptides sold as “research retatrutide” are not the investigational product used in TRIUMPH. Supply of an unlicensed product for human administration is a medicines-law question, not a dietary-supplement question. Peptide Data frames all such compounds as research-use-only. This article does not authorise, describe or recommend personal use.

8. What these data do not show

Several limits follow directly from the disclosure:

  • The results are topline. Confidence intervals, p-values, responder analyses (≥5%, ≥10%, ≥15%, ≥20% weight loss), treatment-regimen estimands, body-composition data and the nested OSA endpoints in TRIUMPH-2 have not been released.[1][2]
  • TRIUMPH-2 and TRIUMPH-3 were placebo-controlled. They do not rank retatrutide against tirzepatide or semaglutide. A head-to-head trial remains outstanding.
  • TRIUMPH-3 does not answer the cardiovascular-outcomes question. MACE hazard ratios are compatible with benefit, harm or no effect.
  • Five positive Phase 3 studies, as counted by the sponsor, are not the same as a completed regulatory review. CMC, inspection, labelling and risk-management requirements can still delay or prevent authorisation.[1]
  • Phase 2 data published in the New England Journal of Medicine in 2023 remain the last fully peer-reviewed efficacy paper. They are not superseded by a press release.[7]

For researchers tracking the incretin class, the useful facts are narrower: in two additional 80-week Phase 3 trials, a triple GIP/GLP-1/glucagon agonist produced double-digit mean percent weight loss in populations that are typically harder to move (type 2 diabetes; severe obesity with established CVD), with a gastrointestinal and dysesthesia profile that will need full tables before any safety conclusion is stable. That is the evidence. It is not a UK licence, and it is not a basis for unlicensed human use.

This article is for research and educational purposes only. Retatrutide is an investigational compound, not licensed for human use in the UK. Nothing in this article is medical advice, consumption advice, or a dosing instruction.

This article is AI-researched and editorially reviewed. It is provided for research and educational purposes only and is not medical advice. Research peptides are not licensed for human consumption in the UK.