TRIUMPH-4 in NEJM: What Retatrutide's Knee Osteoarthritis Trials Show

What happened / Why it matters

What happened. Retatrutide is an experimental drug. It is not FDA-approved for any use. The results of TRIUMPH-4 and TRIUMPH-1-OA were published in the New England Journal of Medicine on Nov. 8, 2026. The journal says they were presented in part at the American College of Rheumatology’s annual meeting.

Why it matters. This is the first peer-reviewed publication of a phase 3 retatrutide trial dedicated to knee osteoarthritis. Eli Lilly, which makes retatrutide, first reported the main results in December 2025. The journal’s main analysis shows a pain benefit of about 1.6 to 1.8 points on a 0-to-10 scale compared with placebo. The status of the drug does not change: see our page on whether retatrutide is FDA-approved.

What did the trial find?

TRIUMPH-4 enrolled 445 adults without diabetes who had painful knee osteoarthritis and a body-mass index of at least 27. After 68 weeks, scores on the WOMAC pain scale (0 to 10) fell by 3.96 and 3.74 points on the two retatrutide doses and by 2.12 points on placebo. That is a difference of about 1.6 to 1.8 points, in the journal’s main analysis.

Body weight fell 20.0% and 23.7% on retatrutide, compared with 4.6% on placebo.

Here is how the NEJM abstract reports the pain results in TRIUMPH-4, in points on the 0-to-10 scale, relative to placebo:

Pain scores fell slightly less on the higher dose (3.74 points) than on the lower one (3.96 points). The doses are the trial’s design, not a recommendation.

Why do Lilly’s headline numbers differ?

Lilly’s earlier figures, a drop of about 4.4 to 4.5 points, came from a different analysis that assumes people stayed on treatment. The same December 2025 release also gave figures from a treatment-regimen analysis: a drop of 4.0 and 3.7 points on retatrutide and 2.1 points on placebo, close to the journal’s. The journal’s main analysis for pain uses what it calls a hybrid-treatment estimand: one statistical method for events that suggested the treatment had failed and, for everything else, people’s results whether or not they kept taking the drug. It is not the efficacy analysis Lilly used for its headline figures. We use the journal’s figure as the main result because it is the peer-reviewed one. For the same reason, we do not repeat the “percent less pain” figure Lilly used in 2025.

People on placebo also improved, by 2.12 points, which is more than half the improvement seen on retatrutide.

What is TRIUMPH-1-OA?

TRIUMPH-1-OA is not a separate trial. It covers the 574 people with knee osteoarthritis who took part in the larger TRIUMPH-1 obesity trial. TRIUMPH-1 itself was published in NEJM in September, and we reported its results then. The new paper reports this group’s pain results in full: at 80 weeks, the main-analysis difference from placebo was −1.35, −1.61 and −1.77 points across the three retatrutide doses, and −0.96, −1.41 and −1.64 points in the intention-to-treat analysis. These match the rounded figures from the earlier TRIUMPH-1 paper.

What about side effects?

In both trials, serious adverse events were more common with retatrutide than with placebo, and the most common side effects were gastrointestinal, according to the journal’s abstract.

On stopping treatment, we have only company data. In its December 2025 release, Lilly reported that 12.2% and 18.2% of people on the two retatrutide doses in TRIUMPH-4 stopped because of adverse events, compared with 4.0% on placebo. We have not confirmed those numbers against the full journal text.

What do the trials not show?

The NEJM abstract reports pain, body weight and safety. It does not report whether retatrutide changed the knee joint itself, and we did not read the full text.

Who paid for the trials?

Both trials were funded by Eli Lilly, which makes retatrutide; five of the 10 authors are affiliated with the company.

What is retatrutide’s regulatory status?

Retatrutide is not FDA-approved. A search of FDA’s Drugs@FDA data on Nov. 8 found no product listed under that name. Lilly says it plans to submit an application to FDA in the first quarter of 2027, which is a company plan and not an FDA decision. FDA says retatrutide cannot be used in compounding under federal law. For the full status and a dated change log, see our status page. For the evidence guide, see Best Peptides For’s page on retatrutide.

What does this mean for a reader?

One trial, funded by the maker of the drug, shows a modest pain benefit over placebo in people with knee osteoarthritis and obesity or overweight, and it has not shown an effect on the disease itself. People with knee pain can talk with a clinician about approved options. We do not link to or recommend sellers, and we give no dosing guidance.

U.S. regulatory status checked Nov. 8, 2026. Based on the journal’s abstract and notes; we did not read the full text or the appendix.