Retatrutide in Phase 3: What TRIUMPH-2 Showed at EASD 2026

What TRIUMPH-2 is

TRIUMPH-2 (NCT05929079) is one of the four registrational trials in the Phase 3 TRIUMPH program, in which Eli Lilly is evaluating retatrutide, its triple agonist of the GIP, GLP-1 and glucagon receptors. It studied the hardest population for this class of molecules: adults with obesity or overweight and type 2 diabetes, a group that, trial after trial, loses less weight than people without diabetes.

• 1,152 adults at 92 sites in 8 countries, randomly assigned to retatrutide 4 mg, 9 mg or 12 mg once weekly, or placebo, for 80 weeks (double-blind).
• Starting point: mean body weight 106.4 kg, mean body-mass index (BMI) 38.2 kg/m² and mean glycated hemoglobin (A1C) 7.7%. 92% were already on oral glucose-lowering medication.
• Primary endpoint of the trial: percent change in body weight at week 80 versus placebo, for the 9 mg and 12 mg doses (4 mg was a key secondary endpoint).
• Funded by Eli Lilly. The first author of the publication is Virginia Bellido, of Virgen del Rocío University Hospital (Seville, Spain).

Lilly released the topline figures on July 23, 2026. The full results were presented on September 30 at the annual meeting of the European Association for the Study of Diabetes (EASD) in Milan, and published in The Lancet (online from September 29).

The results: weight and A1C

These are the TRIUMPH-2 trial figures at 80 weeks, per Lilly's September 29, 2026 press release:

Source: Eli Lilly, TRIUMPH-2 trial results (efficacy estimand). Mean baseline A1C: 7.7%.

According to Lilly, 59.5% of participants in the 12 mg arm no longer met the BMI criteria for obesity at the end of the trial, and in the subgroup starting from a BMI of 35 or higher the mean reduction on 12 mg was 23.4%. The company also reports improvements in cardiometabolic risk factors on 12 mg: triglycerides −39.5%, non-HDL cholesterol −19.6%, systolic blood pressure −10.8 mmHg and waist circumference −16.9 cm.

Two numbers for one trial: 20.8% and 18.8%

Lilly's headline says −20.8%. The primary figure in the Lancet paper is −18.8%. Both are correct: they answer different questions.

• Efficacy estimand (−20.8%): how much weight changes if the participant stays on treatment for all 80 weeks of the trial.
• Treatment-regimen estimand (−18.8%): the average across everyone assigned to that arm, including those who stopped. This is the trial's primary analysis.

Under that second analysis, the change in body weight in the trial was −11.9% (4 mg), −16.8% (9 mg) and −18.8% (12 mg), versus −5.1% on placebo. The difference versus placebo on 12 mg was −13.8 percentage points (95% CI: −15.8 to −11.8).

When you read a headline about this class of compounds, ask which of the two numbers you are looking at. Press releases tend to lead with the first; the primary analysis — and any honest comparison across trials — uses the second.

Safety and tolerability

The authors describe the trial's safety profile as "generally consistent with other molecules with GLP-1 receptor agonism." The most frequent adverse events were gastrointestinal:

Source: Eli Lilly, TRIUMPH-2 trial results.

Four details worth not skipping:

• Dysesthesia. Altered skin sensation (tingling, heightened sensitivity to touch) occurred in up to 7.3% of participants on retatrutide versus 0.7% on placebo. In TRIUMPH-1, the trial in people without diabetes, it reached 12.5% on 12 mg. Lilly describes these events as generally mild to moderate, with the majority resolving during treatment.
• Hypotension. Per The Lancet, it was more frequent with retatrutide: 1%, 5% and 6% (4, 9 and 12 mg) versus under 1% on placebo.
• Discontinuations. The 9 mg arm had more discontinuations due to adverse events (11.6%) than the 12 mg arm (7.7%).
• Deaths. There were seven during the trial: six in the retatrutide arms and one in the placebo arm. Investigators judged none of them to be related to the study treatment.

What 80 weeks cannot answer is long-term cardiovascular safety. In TRIUMPH-3 — the trial in severe obesity with established cardiovascular disease — the analysis of major adverse cardiovascular events produced hazard ratios of 0.82 (95% CI: 0.55–1.22) and 1.12 (95% CI: 0.64–1.96) depending on the definition used: intervals too wide to conclude either benefit or harm. Lilly is studying cardiovascular and renal outcomes in a separate trial.

Triple vs dual: what the comparison suggests

This is the underlying question: what does the third receptor — glucagon — add over a dual agonist like tirzepatide? No head-to-head trial has been published yet. What can be done is to line up the equivalent trial from each generation, in the same population (obesity or overweight with type 2 diabetes) and using the same type of analysis:

Phase 3 trials in adults with obesity or overweight and type 2 diabetes; analysis of all randomized participants. Sources: The Lancet 2021, 2023 and 2026.

Three readings, from most to least comfortable:

1. The mono → dual → triple progression holds. Each added receptor coincides with a larger reduction in body weight in its trial.
2. The triple's edge over the dual is more modest than the headlines suggest. Comparing each trial's headline figure (−20.8% vs −15.7%), the gap looks like five points. Using the same analysis and subtracting placebo, it is about two: 13.8 vs 11.6. The TRIUMPH-2 trial ran eight weeks longer, and its placebo arm lost more weight than SURMOUNT-2's.
3. On glucose there is no sign of an advantage. In the TRIUMPH-2 trial, A1C fell by up to 1.6 points from a baseline of 7.7%, and up to 40.0% of participants reached below 5.7%. In SURMOUNT-2, tirzepatide lowered it by 2.1 points from 8.0%, and between 50.2% and 55.3% reached below 5.7% (proportions from Lilly's press releases, both under the efficacy estimand). The baselines differ, so the comparison is imperfect. One possible explanation — unproven — is that glucagon agonism stimulates hepatic glucose production and offsets part of the effect.

In people without diabetes the gap observed across trials is somewhat wider. Using the same type of analysis and subtracting placebo: −21.1 points on retatrutide 12 mg at 80 weeks in the TRIUMPH-1 trial, versus −17.8 on tirzepatide 15 mg at 72 weeks in the SURMOUNT-1 trial. About three points.

Comparing different trials is not comparing compounds: populations, duration, baseline values and the handling of missing data all differ. The real answer will come from TRIUMPH-5, the trial pitting retatrutide directly against tirzepatide in about 800 adults with obesity; per ClinicalTrials.gov, its primary completion is estimated for November 2026. The proposed mechanism behind the difference — glucagon agonism raises energy expenditure, on top of the lower intake associated with GLP-1 and GIP — is covered in our retatrutide guide and in Tirzepatide vs Retatrutide.

What is still missing for an approval

Retatrutide is not approved in any country. With the TRIUMPH-1, -2, -3 and -4 trials reported, this is what lies ahead:

1. The filing. Lilly has said it plans to submit a Biologics License Application (BLA) to the FDA in the first quarter of 2027. After TRIUMPH-2 and TRIUMPH-3, the company says it has the clinical data package to support global submissions.
2. The review. A standard FDA review takes on the order of 10 to 12 months from submission, so a decision would come, at the earliest, toward late 2027 or in 2028. That is our estimate based on typical timelines, not a Lilly announcement.
3. The classification. There is an open dispute between Lilly and the FDA over whether retatrutide should be filed as a biological product or as a conventional drug. The difference is years of market exclusivity (12 versus 5). The litigation was still open as of August 2026, per BioSpace; it does not change the clinical data.
4. The data still to come. The obstructive sleep apnea sub-study of TRIUMPH-2; TRIUMPH-5, the direct comparison with tirzepatide; the cardiovascular and renal outcomes trial; and the rest of the TRANSCEND-T2D program in type 2 diabetes, whose first trial reported A1C reductions of up to 2.0 points at 40 weeks in March 2026.
5. After the FDA. Each agency reviews separately. In the Dominican Republic, a medicine needs DIGEMAPS registration before it can be marketed (the framework is in our legality guide), and coverage is a separate discussion: we cover it in GLP-1s in the DR: listed, but still not covered by insurers.

In the meantime, the status has not changed: retatrutide is an investigational molecule, and no regulatory agency has approved it for human use.

What it means (and doesn't) for research

Three things the TRIUMPH-2 trial does not say:

• It does not describe research material. The results belong to Lilly's investigational product, manufactured to pharmaceutical standards and administered inside a clinical trial under medical supervision. They cannot be extrapolated to any other material, including ours.
• It does not make retatrutide an available treatment. Today its only authorized use in people is inside clinical trials.
• It does not replace verification. Outside a trial, a compound's identity and purity are only known through independent analysis. We covered the study that measured the gap between unverified sources and the trials in Black-market retatrutide vs clinical trials.

At Renova, retatrutide is offered solely as a reference material for laboratory research (RUO), not for human or veterinary consumption. This article makes no efficacy claims of its own: every figure comes from published clinical trials or from their sponsors' press releases, and is attributed to its source. What we do publish is the characterization of the material: Janoshik certificates of analysis (HPLC + mass spectrometry) are at /en/coa/.

Sources

• The Lancet — Bellido V, et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2), Sep 29, 2026
• Eli Lilly — full TRIUMPH-2 results (Sep 29, 2026)
• Eli Lilly — EASD 2026 presentations (Sep 15, 2026)
• Eli Lilly — TRIUMPH-2 and TRIUMPH-3 topline (Jul 23, 2026)
• Eli Lilly — TRIUMPH-1 (May 21, 2026)
• Eli Lilly — TRANSCEND-T2D-1 (Mar 19, 2026)
• Eli Lilly — TRIUMPH-4 (Dec 11, 2025)
• SURMOUNT-2 — Garvey WT, et al. The Lancet, 2023 · Lilly press release · ADA press release
• STEP 2 — Davies M, et al. The Lancet, 2021
• SURMOUNT-1 — Jastreboff AM, et al. New England Journal of Medicine, 2022
• ClinicalTrials.gov — TRIUMPH-5 (NCT06662383)
• BioSpace — the Lilly–FDA classification dispute (Aug 5, 2026)
• Pharmacy Times — coverage of the TRIUMPH-2 results (Sep 30, 2026)