Retatrutide Phase 3 NEJM: Reading the TRIUMPH Trial Data

Direct answer: Retatrutide's Phase 3 program is called TRIUMPH and consists of multiple trials in obesity, type 2 diabetes, cardiovascular disease, and other indications. TRIUMPH-4 reported topline results in December 2025: 26.6% placebo-adjusted body weight loss at 12mg over 68 weeks — the highest Phase 3 obesity drug result ever published. TRIUMPH-1 and TRIUMPH-2 have ongoing data releases. The full peer-reviewed NEJM publication of Phase 3 results is anticipated through 2026. The published Phase 2 data (NEJM 2023, Jastreboff et al.) remains the most-cited reference until Phase 3 papers land.

Key Takeaways

• TRIUMPH is Eli Lilly's Phase 3 trial program for retatrutide — a series of trials, not a single study.
• TRIUMPH-4 topline (Dec 2025): 26.6% placebo-adjusted weight loss at 12mg over 68 weeks.
• Phase 2 NEJM paper (Jastreboff et al., 2023) is the foundational peer-reviewed reference: 24.2% weight loss at 12mg over 48 weeks.
• Sample size: Phase 3 trials enrolled 5,000+ adults combined, vs 338 in Phase 2 — much larger statistical power.
• Trial outcomes confirmed Phase 2: dose-dependent weight loss, dominant GI side effect profile, dysesthesia signal.
• Cardiovascular outcomes (TRIUMPH-3) are still maturing — the trial reads out 2026–2027.
• NEJM publication of Phase 3 data is expected through 2026; preliminary results are in conference presentations and corporate press releases.

What "Phase 3" Means for a Drug Trial

The FDA drug approval process has three phases of human trials:

• Phase 1: Small (10–100 subjects) safety + dosing trials in healthy volunteers
• Phase 2: Mid-sized (100–500 subjects) efficacy + dose-finding trials in patients
• Phase 3: Large (1,000–10,000+ subjects) confirmatory efficacy + safety trials in patients

A drug needs successful Phase 3 results to file a New Drug Application (NDA) with the FDA. Phase 3 is where most drug development programs fail — the bigger sample size exposes safety or efficacy issues that smaller Phase 2 trials missed.

Retatrutide's Phase 3 program — TRIUMPH — is what Eli Lilly is currently running and what determines whether retatrutide reaches the market.

The TRIUMPH Program: All Phase 3 Trials at a Glance

Lilly designed TRIUMPH as a portfolio of Phase 3 trials covering different patient populations and indications. The major trials:

The trial Lilly is most likely to file its NDA on is TRIUMPH-1 + TRIUMPH-2 for obesity and T2D indications respectively. TRIUMPH-3 (cardiovascular outcomes) reads out later and supports the cardioprotective label expansion.

TRIUMPH-4 Headline Result (December 2025)

TRIUMPH-4 was the first Phase 3 retatrutide trial to report topline results. The headline numbers:

• Population: ~2,500 obese adults (BMI ≥30 or ≥27 with comorbidity)
• Doses tested: placebo, 3mg, 6mg, 9mg, 12mg weekly
• Duration: 68 weeks
• Primary endpoint: Percent change in body weight from baseline

Results at 12mg:

• Mean weight loss (absolute): ~24.5% from baseline (~71 lbs average)
• Placebo-adjusted weight loss: 26.6% (placebo lost ~2%)
• Responder rate (≥10% weight loss): 81% of 12mg arm
• Responder rate (≥20% weight loss): 64% of 12mg arm
• Discontinued due to AE: 14% (vs 3% on placebo)

The 26.6% figure is the highest Phase 3 obesity drug result ever published — surpassing semaglutide's 14.9% (STEP-1) and tirzepatide's 22.5% (SURMOUNT-1).

Phase 2 NEJM Paper: The Foundational Reference

Until Phase 3 papers are peer-reviewed and published, the Phase 2 paper in NEJM remains the most-cited retatrutide reference:

Citation: Jastreboff AM, Kaplan LM, Frías JP, et al. "Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial." N Engl J Med 2023;389:514-526. DOI: 10.1056/NEJMoa2301972.

Key details:

• Design: Randomized, double-blind, placebo-controlled
• N = 338 adults with BMI ≥30 (or ≥27 with comorbidity)
• Doses: placebo, 1mg, 4mg, 8mg, 12mg weekly
• Duration: 48 weeks
• Primary endpoint: Percent change in body weight at week 24 and week 48

Headline results at 48 weeks:

This paper established that retatrutide produces dose-dependent weight loss far exceeding semaglutide and tirzepatide at comparable trial protocols. The Phase 3 TRIUMPH-4 result (26.6%) confirmed the Phase 2 finding at larger sample size, with the small additional weight loss likely due to the longer 68-week trial duration.

How TRIUMPH-4 Differs from Phase 2

The slower TRIUMPH-4 titration (starting at 0.5mg vs Phase 2's 2mg) was specifically designed to reduce GI dropout, and it worked — discontinuation rates dropped from 16% to 14% at the same maintenance dose.

When Will the Phase 3 NEJM Paper Be Published?

As of May 2026:

• TRIUMPH-4 topline: Released December 2025 (corporate press release + investor presentation)
• TRIUMPH-4 full results: Presented at ADA Scientific Sessions June 2026 (anticipated)
• TRIUMPH-4 NEJM paper: Submission expected mid-2026, publication likely late 2026
• TRIUMPH-1 and TRIUMPH-2: Topline 2025–2026; full publication 2026–2027
• TRIUMPH-3 (CV outcomes): Ongoing; readout expected 2027

Eli Lilly's typical pattern is: topline → conference presentation → NEJM publication, spanning 6–12 months. So expect the TRIUMPH-4 full NEJM paper around Q4 2026.

Phase 3 Trial Data: What's Publicly Available Right Now

Until the NEJM papers land, here's what you can access for Phase 3 retatrutide data:

• Eli Lilly investor presentations (quarterly earnings calls and ADA-timed releases) — corporate-format summaries
• Press releases (Lilly newsroom) — top-line results
• ClinicalTrials.gov entries for each TRIUMPH trial — protocol details, primary/secondary endpoints, enrollment status
• Conference presentations (ADA, EASD, ObesityWeek) — peer-reviewed posters and oral presentations
• TRIUMPH-4 preliminary publications — interim analyses may appear in subspecialty journals before full NEJM release

For the most rigorous-format reading, conference presentation abstracts and ClinicalTrials.gov entries are the closest you can get to "Phase 3 data you can cite."

How Retatrutide Phase 3 Data Compares to Semaglutide and Tirzepatide

The three drugs have Phase 3 obesity trials structured similarly enough to compare directly:

The progression is striking: each successive triple-/dual-/single-agonist tier produces 4–8 additional percentage points of weight loss. This is the strongest case for retatrutide as a category-defining drug — and what's driving the regulatory and commercial interest.

Reading Phase 3 Data Critically

If you're going to evaluate retatrutide Phase 3 results, a few caveats worth keeping in mind:

1. Trial populations are filtered. Phase 3 patients are screened for comorbidities, motivated to comply, and supported by trial staff. Real-world response rates run lower.
2. Placebo arms also lose weight. TRIUMPH-4's 2% placebo loss reflects diet + lifestyle counseling provided to all participants. Real-world placebo responses to no intervention would be flat or trending up.
3. Discontinuation matters. A 14% AE-driven discontinuation rate means roughly 1 in 7 trial participants stopped the drug — these patients' weights at discontinuation get carried forward in some analyses but not others.
4. Open-label extension data is needed to know weight maintenance beyond 68 weeks.
5. Cardiovascular outcomes (TRIUMPH-3) are essential for the full safety picture, especially for older or comorbid patients.

For the headline weight loss claim — "retatrutide produces 26.6% weight loss" — to be accurate in your decision-making, you should be:

• Eligible based on Phase 3 inclusion criteria (or similar BMI + age + comorbidity profile)
• Willing to titrate over 6+ months
• Able to tolerate or manage GI symptoms during titration
• Not at risk of contraindications (pancreatitis history, MTC family history, pregnancy)

For our deeper coverage of the clinical trial results, see retatrutide 2026: what the data actually show and retatrutide clinical trial results.

Frequently Asked Questions

Has retatrutide Phase 3 been published in NEJM yet? As of May 2026, no full Phase 3 paper has been published in NEJM. Topline results from TRIUMPH-4 were released in December 2025 via corporate press release. Full peer-reviewed publication is anticipated through 2026, likely Q4. The Phase 2 NEJM paper (Jastreboff et al., 2023) remains the most-cited published reference.

What did the retatrutide Phase 3 results show? TRIUMPH-4 (Dec 2025) showed 26.6% placebo-adjusted body weight loss at the 12mg weekly dose over 68 weeks. Responder rates: 81% achieved ≥10% weight loss, 64% achieved ≥20%. Adverse event-driven discontinuation was 14% at 12mg vs 3% on placebo.

Where can I read the retatrutide trial data? For the published Phase 2 data: NEJM 2023, Jastreboff et al. (nejm.org/doi/full/10.1056/NEJMoa2301972). For Phase 3 TRIUMPH-4 results, see Eli Lilly's December 2025 investor presentation and the upcoming ADA Scientific Sessions June 2026 presentations. Full NEJM publication expected late 2026.

What is the TRIUMPH program? TRIUMPH is Eli Lilly's Phase 3 clinical trial program for retatrutide, consisting of multiple trials in different patient populations — obesity (TRIUMPH-1, -4), type 2 diabetes (TRIUMPH-2), cardiovascular disease (TRIUMPH-3), osteoarthritis (TRIUMPH-OA), and liver disease (TRIUMPH-Liver). Each trial supports a different potential FDA indication.

How is retatrutide research different from semaglutide and tirzepatide research? The clinical trial structure is similar (randomized, placebo-controlled, 68+ week duration), but retatrutide adds the third receptor target (glucagon) which produces measurably more weight loss. The Phase 3 data so far suggests retatrutide produces 4–8% more weight loss than tirzepatide at equivalent trial designs.

What are the retatrutide studies on cardiovascular outcomes? TRIUMPH-3 is the dedicated Phase 3 cardiovascular outcomes trial. It enrolls patients with established cardiovascular disease + obesity and tracks major adverse cardiovascular events (MACE) over multi-year follow-up. Readout is anticipated 2027. Until then, cardiovascular safety conclusions about retatrutide are extrapolated from class data (semaglutide's SELECT trial).

What journals have published retatrutide research?

• NEJM (2023): Phase 2 weight loss trial (Jastreboff et al.) — the foundational paper
• NEJM (2023): Phase 2 T2D trial (Rosenstock et al.) — companion paper
• Diabetes Care (2024+): Subgroup analyses and mechanism papers
• Lancet Diabetes & Endocrinology: Additional analyses expected

Phase 3 publications will likely also concentrate in NEJM, Lancet, and high-impact obesity/endocrinology journals.

Are the retatrutide trials still recruiting? Some TRIUMPH trials (especially TRIUMPH-3 cardiovascular outcomes and TRIUMPH-Liver) are still recruiting as of 2026. ClinicalTrials.gov has current enrollment status. The obesity and T2D trials (TRIUMPH-1, -2, -4) closed enrollment in 2024–2025.

Medical Disclaimer: Retatrutide is an investigational compound not FDA-approved for any indication as of 2026. This article summarizes published and presented Phase 2 and Phase 3 clinical trial data for educational purposes only. Trial design specifics, sample sizes, and outcomes may be updated as full peer-reviewed publications appear. Consult primary literature (NEJM, Lancet, ClinicalTrials.gov) for the most current data. This article does not constitute medical advice.