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Retatrutide Phase 3 (TRIUMPH): results so far, including knee osteoarthritis

Reviewed 27 October 2026 · For laboratory research and education only

Research use only · Not medical advice

Retatrutide (LY3437943) is Eli Lilly's investigational once-weekly peptide that acts on three receptors: GIP, GLP-1 and glucagon. The retatrutide Phase 3 program for obesity is called TRIUMPH, and by October 2026 every one of its four registrational trials had shared topline numbers. Below we pull together what Lilly and ClinicalTrials.gov have released, starting with TRIUMPH-4 in knee osteoarthritis, then look at the limits of the data and where the filing stands. For the compound itself, see our retatrutide profile.

In short

The knee osteoarthritis study, TRIUMPH-4, hit both of its co-primary goals (weight and WOMAC pain) against placebo.
All four TRIUMPH trials are complete; most numbers are still company toplines, not peer-reviewed papers.
TRIUMPH-3 could not settle the cardiovascular question: too few heart events occurred.
No regulator has approved retatrutide. Lilly's US filing is planned for Q1 2027, so there is no approval date yet.

The four TRIUMPH trials at a glance

Every trial below was randomized, double-blind and placebo-controlled, and every one is listed as completed on ClinicalTrials.gov. Figures are the weight changes Lilly reported for the highest-dose arm against placebo using the efficacy estimand (participants who stayed on treatment), unless noted.

Trial	Population	Size / length	Headline result (highest arm vs placebo)	Reported
TRIUMPH-4 NCT05931367	Obesity or overweight with knee osteoarthritis, no diabetes	445 / 68 weeks	Weight −28.7% vs −2.1%; WOMAC pain −74.3% vs −40.3%	11 Dec 2025
TRIUMPH-1 NCT05929066	Obesity or overweight with a weight-related condition, no diabetes	2,339 randomized / 80 weeks	Weight −28.3% vs −2.2%	21 May 2026
TRIUMPH-2 NCT05929079	Type 2 diabetes with obesity or overweight	1,152 / 80 weeks	Weight −20.8% vs −4.0%; A1C down up to 1.6 points vs 0.2	23 Jul 2026
TRIUMPH-3 NCT05882045	BMI ≥35 with established cardiovascular disease	1,949 / 80 weeks	Weight −22.6% vs −3.2%	23 Jul 2026

These numbers come from different populations and trial lengths, so they should not be compared head to head. Weight loss was smaller in the type 2 diabetes trial, a pattern also seen with other incretin-based medicines.

TRIUMPH-4: the knee osteoarthritis trial

TRIUMPH-4 was the first Phase 3 retatrutide trial to read out. It enrolled 445 adults with obesity or overweight and knee osteoarthritis, without diabetes, and randomized them equally to two retatrutide arms or placebo for 68 weeks. Average baseline weight was 112.7 kg and 84% of participants had a BMI of 35 or more. ClinicalTrials.gov lists its primary completion date as 14 November 2025.

The trial had two co-primary endpoints: percent change in body weight, and change in the WOMAC pain subscale, a standard questionnaire used in osteoarthritis research. Lilly reported that both retatrutide arms met both endpoints and all key secondary endpoints:

Endpoint at 68 weeks (efficacy estimand)	Lower retatrutide arm	Higher retatrutide arm	Placebo
Body weight change	−26.4%	−28.7%	−2.1%
WOMAC pain change	−75.8%	−74.3%	−40.3%
WOMAC physical function change	−71.8%	−73.7%	−35.6%
Discontinued due to adverse events	12.2%	18.2%	4.0%

Two details matter for interpretation. First, the placebo group also reported a sizeable pain reduction (about 40%), which is common in pain trials and is why the placebo comparison is essential. Second, under the treatment-regimen estimand, which counts everyone regardless of whether they stopped treatment, the effects were smaller: weight change of −20.0% and −23.7% versus −4.6% for placebo. TRIUMPH-1 also included a knee osteoarthritis basket, and in June 2026 Lilly reported WOMAC pain reductions of up to 73.1% from baseline in that sub-study.

The trial measured symptoms (pain and function scores), not joint structure. It does not show that retatrutide changes cartilage or slows osteoarthritis progression, and the results have been released as topline data rather than a full peer-reviewed paper.

TRIUMPH-1: the main obesity trial

TRIUMPH-1 is the largest trial in the program. It randomized 2,339 adults with obesity or overweight and at least one weight-related condition, without diabetes, to three retatrutide arms or placebo for 80 weeks. Lilly announced topline results on 21 May 2026 and presented more at the American Diabetes Association's 86th Scientific Sessions on 6 June 2026.

Mean weight change ranged from −19.0% to −28.3% across the retatrutide arms, versus −2.2% for placebo. A 104-week extension in 532 participants with a baseline BMI of 35 or more reported changes of up to −30.3%, although the placebo group in that extension was switched to retatrutide. The master trial also contained an obstructive sleep apnea basket, where Lilly reported reductions in the apnea-hypopnea index of up to 60.6% from a high baseline.

TRIUMPH-2 and TRIUMPH-3

Lilly released both results together on 23 July 2026. TRIUMPH-2 enrolled 1,152 adults with type 2 diabetes and obesity or overweight. Weight change ranged from −12.7% to −20.8% across arms versus −4.0% for placebo, and A1C fell by up to 1.6 percentage points from a 7.7% baseline, versus 0.2 for placebo.

TRIUMPH-3 enrolled 1,949 adults with a BMI of 35 or more and established cardiovascular disease. Weight change was −21.6% and −22.6% in the two retatrutide arms versus −3.2% for placebo. The trial also tracked major adverse cardiovascular events, but the comparisons were not statistically significant: 44 versus 52 events for the five-component measure (hazard ratio 0.82, 95% CI 0.55 to 1.22) and 27 versus 23 for the three-component measure (hazard ratio 1.12, 95% CI 0.64 to 1.96). Lilly said events were less frequent than expected in both groups, so this trial cannot answer whether retatrutide affects cardiovascular risk.

Safety signals reported so far

Across the trials, the most common adverse events were gastrointestinal: nausea, diarrhea, constipation and vomiting, which Lilly describes as mostly mild to moderate and consistent with other incretin-based medicines. Two other signals appear repeatedly:

Dysesthesia (abnormal skin sensation) was reported in up to 20.9% of participants on retatrutide in TRIUMPH-4 versus 0.7% on placebo, and in up to 12.5% versus 0.9% in TRIUMPH-1. Lilly says it was generally mild.
Discontinuation due to adverse events was higher on retatrutide than placebo in most trials, reaching 18.2% in the higher TRIUMPH-4 arm. Lilly said those rates tracked baseline BMI and included people who stopped for perceived excessive weight loss.

Longer-term safety, and safety outside tightly monitored trial settings, is still unknown.

Retatrutide approval date: where things stand

Lilly's own releases call retatrutide investigational, and it holds no FDA, EMA or MHRA approval. On its Q2 2026 earnings call, Lilly said it plans to submit a Biologics License Application in the US in the first quarter of 2027, after completing its chemistry, manufacturing and controls package. Lilly has also said it has the clinical data to support global submissions for obesity, knee osteoarthritis pain and obstructive sleep apnea. Sites quoting a firm approval date are guessing; none has been announced.

The approved medicines in this class today are different products. Tirzepatide, for example, is FDA-approved as Mounjaro for type 2 diabetes and as Zepbound for chronic weight management. Research-grade retatrutide powder sold online is not Lilly's trial medicine, has not been approved by any regulator, and is not for human use. If you work with research material, our guides on checking a peptide certificate of analysis and FDA warning letters to peptide sellers explain what to look for. Our semaglutide vs tirzepatide vs retatrutide comparison covers how the three molecules differ, and the peptide library lists every compound we profile, including tirzepatide and semaglutide.

What is still to come

Peer-reviewed publication of full TRIUMPH results (a companion diabetes trial, TRANSCEND-T2D-1, was published in The Lancet in June 2026).
More TRANSCEND-T2D diabetes results, which Lilly expects over the coming year, and a chronic low back pain study that Lilly expects to read out in 2027.
Separate cardiovascular/renal outcomes and liver disease (MASLD) studies.
The US filing in Q1 2027, followed by FDA review.

Related peptide profiles and guides

Retatrutide compound profile: sequence, molecular weight and regulatory status
Tirzepatide compound profile
Semaglutide compound profile
Semaglutide vs tirzepatide vs retatrutide: the three incretin peptides compared
FDA peptide advisory vote, July 2026
Full research peptide library

FAQ

Is retatrutide FDA approved?

No. It remains an investigational drug in the US, UK and EU. The first US submission is planned for early 2027.

What did the TRIUMPH-4 trial measure?

Two things at 68 weeks: percent change in body weight and change in the WOMAC knee pain score, each compared with placebo in people with knee osteoarthritis and excess weight.

What is the WOMAC score?

WOMAC is a standardized osteoarthritis questionnaire. TRIUMPH-4 used its pain subscale as a co-primary endpoint and also reported its physical function subscale.

Did TRIUMPH-3 prove a heart benefit?

No. Event counts were low in both groups and the hazard ratios had wide confidence intervals that crossed 1, so the result is inconclusive.

Does TRIUMPH-4 show cartilage repair?

No. It tracked symptoms reported by participants, not imaging of the joint, so it cannot speak to cartilage or disease progression.

Is research-grade retatrutide the trial medicine?

No. Lilly's trial product is made under clinical manufacturing controls. Powder sold for research is a different, unapproved material and is not for human use. More on the retatrutide profile.