Retatrutide Knee Pain Results: The TRIUMPH-4 Verdict Lands at ACR 2026

The verdict, in one paragraph

The full TRIUMPH-4 dataset was presented on Sunday, November 8, 2026, at the American College of Rheumatology’s ACR Convergence plenary in Orlando — and published the same day in the New England Journal of Medicine. In 445 adults with painful knee osteoarthritis and obesity, once-weekly retatrutide cut knee pain by an average of 3.7 to 4.0 points on the 10-point WOMAC pain scale over 68 weeks, against 2.1 points on placebo, while body weight fell 20 to 24 percent against 4.6 percent on placebo. The headline figure from Eli Lilly’s November 5 announcement — pain down as much as 75.8 percent — held up as a description of the best result among people who stayed on treatment, but it is a post-hoc calculation, not the trial’s pre-specified result. The pre-specified numbers are smaller, still clearly positive, and come with a real side-effect cost: about one in eight people on the 9 mg dose and nearly one in five on the 12 mg dose stopped treatment because of side effects, mostly stomach and gut problems. Retatrutide remains investigational and is not approved anywhere; Eli Lilly plans to file for FDA approval in the first quarter of 2027.

The numbers at a glance

Sources: Schnitzer et al., New England Journal of Medicine, November 8, 2026 (DOI: 10.1056/NEJMoa2610676); Eli Lilly, November 5, 2026. Pain-free shares are from Lilly’s announcement; the peer-reviewed paper reports responder rates rather than a pain-free share.

What happened today

The countdown ended at 11:15 a.m. ET on Sunday, November 8, when Professor Philip Conaghan of the University of Leeds presented the full TRIUMPH-4 results in Plenary Session I at ACR Convergence 2026 in Orlando (Abstract #0871). The same day, the complete results from both knee osteoarthritis trials — TRIUMPH-4 and TRIUMPH-1-OA, 1,019 participants combined — were published in the New England Journal of Medicine under the title “Retatrutide Once Weekly in Adults with Knee Osteoarthritis Pain and Obesity.”

That same-day peer-reviewed publication is the real news here. When Eli Lilly announced topline results on November 5, the numbers came from a company press release. Today they arrive as a peer-reviewed paper, with the full methods, the pre-specified analyses, the side-effect tables, and the limitations spelled out. The second trial, TRIUMPH-1-OA, was presented the same day in a poster session.

The trials were led by Dr. Thomas Schnitzer of Northwestern University Feinberg School of Medicine, and they were funded by Eli Lilly, which also took part in the design, analysis, and writing. That funding relationship is disclosed in the paper, and it is worth knowing: the sponsor was involved, though the authors state Lilly could not veto publication.

Did the headline numbers hold up?

Short answer: yes in direction, with an important correction in size. Here is the honest version of what changed between the November 5 announcement and the November 8 peer-reviewed paper.

The 75.8 percent figure is real, but it is not the trial’s main result. Lilly’s announcement said pain fell “by up to an average of 4.5 points (75.8%) from an average baseline of 6.0.” The percentage was calculated after the fact — a post-hoc analysis, as Lilly’s own endnote states. Percent change in the WOMAC pain score was not a pre-specified endpoint. The pre-specified result is the change in points: on the analysis the trial was designed around, pain fell 3.96 points on 9 mg and 3.74 points on 12 mg, against 2.12 points on placebo. That is a difference of 1.6 to 1.8 points in favour of retatrutide, and it is highly statistically significant (p < 0.001). The “up to 4.5 points” figure comes from a different analysis — the one that counts only people who stayed on treatment as intended. Both numbers are legitimate; they answer different questions. The 4.5-point figure describes the best-case experience. The 3.7-to-4.0-point figure describes the average experience across everyone who was randomized, including people who stopped treatment.

The weight-loss headline needs the same translation. Lilly’s announcement put weight loss at 26 to 29 percent. The peer-reviewed paper’s primary weight analysis — the treatment-regimen analysis, which counts everyone randomized regardless of whether they finished treatment — gives 20.0 percent on 9 mg and 23.7 percent on 12 mg, against 4.6 percent on placebo. The 26.4 and 28.7 percent figures are the on-treatment numbers. Again, same pattern: the headline describes people who stayed on the drug; the pre-specified analysis describes everyone who started it. Either way, the weight loss is far beyond what diet and exercise alone typically achieve, and far beyond the 10 to 20 percent range seen with currently approved GLP-1 drugs.

The pain-free claim stands as announced. Lilly said more than one in eight people on retatrutide in TRIUMPH-4 ended the trial with no knee pain, and more than one in six in the 80-week trial. Those shares come from the company’s announcement rather than the peer-reviewed paper’s main text, which reports responder rates instead — but the responder rates point the same way. Pooled across both trials, 63 to 70 percent of people on retatrutide had at least half their pain gone by week 68, against 38 percent on placebo. Physical function improved by at least half in 64 to 65 percent on retatrutide, against 33 percent on placebo.

So the verdict is: the headline held up, and the fine print makes it smaller but not small. A 1.6-to-1.8-point extra pain reduction on a 10-point scale, with roughly two in three people cutting their pain in half, is a large effect for knee osteoarthritis — larger, on the paper’s own comparison, than what maximum-dose ibuprofen, tramadol, steroid injections into the joint, or semaglutide have shown in their own trials.

The second trial: TRIUMPH-1-OA

TRIUMPH-4 was not a one-off. A second, independent trial — TRIUMPH-1-OA — ran in parallel with 574 participants over 80 weeks, testing three doses (4, 9, and 12 mg) against placebo. It found the same thing: pain fell 3.2 to 3.6 points on retatrutide against 1.9 points on placebo, and weight fell 17.5 to 24.8 percent against 4.3 percent.

Replication across two independent populations is what turns a striking result into a believable one. Both trials enrolled the same kind of participant — adults with moderate-to-severe knee pain for more than 12 weeks, X-ray evidence of osteoarthritis, a body mass index of 27 or higher plus at least one obesity-related complication, and no diabetes — and both were run across North America, Europe, and Australia. About 80 percent of participants in both trials had a BMI above 35. Women made up roughly 70 percent of participants by design, with enrolment capped to keep men represented.

One naming point worth clearing up: the broader TRIUMPH-1 program is a large obesity trial of 2,339 adults whose results were published in the New England Journal of Medicine in late September 2026. TRIUMPH-1-OA is the knee osteoarthritis trial nested inside that program, with 574 participants. When Lilly’s November 5 announcement talked about “TRIUMPH-1” knee-pain results, it meant the osteoarthritis trial reported here.

How big is the effect, really?

Pain scores are hard to feel in the abstract, so the paper puts retatrutide’s effect next to the effects of treatments people already use. The comparison uses Cohen’s d, a standard measure of effect size:

• Retatrutide: effect size 0.55 to 0.79 across the two trials
• Maximum-dose ibuprofen: 0.37
• Maximum-dose tramadol: 0.31
• Steroid injection into the knee: 0.61
• Semaglutide 2.4 mg (the earlier knee osteoarthritis trial): 0.50

Retatrutide sits above all of them. The semaglutide comparison is the most direct: in that 2024 trial, 65.2 percent of people on semaglutide had at least half their pain gone by week 68 — very close to retatrutide’s 63 to 70 percent. The difference is that retatrutide produced substantially more weight loss alongside a similar pain response, and its effect size on pain was larger.

For scale, the paper notes that a low-calorie diet alone has been shown to cut knee pain by about 34 percent, and bariatric surgery by about 63 percent with 28 percent weight loss. Retatrutide’s pain reduction sits between diet and surgery — without an operation. That framing matters because the mechanism is probably mostly the weight loss itself: every pound of body weight lost takes roughly four pounds of load off the knee with each step. The researchers also note that the drug may reduce inflammation in the joint, but that part is not proven — the mechanism behind the pain relief is, in their words, incompletely understood.

The weight-loss side of the story

It is easy to treat the weight loss as a side note. In these trials it is half the story. Participants started with an average body mass index well into the obese range, and the weight loss on retatrutide was large by any standard: one in four participants on the 12 mg dose in TRIUMPH-4 lost at least 25 percent of their body weight, and a small number lost 100 pounds (45 kilograms) or more.

The weight loss matters for knees in a direct, mechanical way. Excess weight increases the load on weight-bearing joints with every step, and that added stress accelerates cartilage breakdown. Clinical guidelines already list weight reduction alongside exercise and pain medication as a core part of knee osteoarthritis care — the problem has always been that losing more than 10 percent of body weight through diet and exercise alone is difficult, and difficult to sustain, especially when knee pain makes exercise itself painful. That is the trap these trials are aimed at: pain stops movement, lack of movement stops weight loss, and weight keeps the pain going.

There is a catch the paper is careful about. The weight loss came with the usual trade-off of this drug class: loss of muscle mass alongside fat. The lead author, Dr. Schnitzer, noted that muscle helps stabilize the knee, and that diet and exercise remain the first step — cheaper, and without the drug’s side effects. The trial’s own body-composition data, from a separate substudy, suggested fat was lost preferentially over lean mass, but muscle loss remains a real consideration, and it is one reason the researchers stress that this is not a replacement for movement and strength work.

Side effects and dropouts: the part the headline skips

No honest account of TRIUMPH-4 can stop at the pain scores. The side effects were common, dose-dependent, and the reason a substantial minority of participants left the trials.

The most common side effects were stomach and gut problems. Nausea affected 38 percent of people on 9 mg and 43 percent on 12 mg, against 11 percent on placebo. Diarrhoea affected 35 and 33 percent, against 13 percent on placebo. Constipation affected 22 and 25 percent, against 9 percent. Vomiting affected 20 and 21 percent — against nobody on placebo. Most of these events were mild to moderate and clustered during the dose-escalation period, when the dose was being stepped up every four weeks. That pattern will be familiar to anyone who follows this drug class: the gut effects are worst early and tend to settle.

One in eight to nearly one in five people stopped treatment because of side effects. In TRIUMPH-4, discontinuation due to adverse events was 12.2 percent on 9 mg and 18.2 percent on 12 mg, against 4.0 percent on placebo. In TRIUMPH-1-OA it was 2.8 percent on 4 mg, 8.4 percent on 9 mg, and 15.3 percent on 12 mg, against 6.3 percent on placebo. About half of the discontinuations in TRIUMPH-4 were due to gut events. Discontinuation was also linked to starting body mass index in an unusual way: people who started leaner were more likely to stop, including some who stopped because of perceived excessive weight loss. Overall, only 71.9 percent of TRIUMPH-4 participants finished the full 68 weeks of treatment.

There was one new side effect to watch. Tingling, numbness, or pins-and-needles sensations — dysesthesia — occurred in 6.3 to 20.9 percent of people on retatrutide, against 0.7 percent on placebo. The events were generally mild and rarely led to anyone stopping treatment, but this had not been a feature of earlier retatrutide trials, and it is the kind of signal that needs watching as more data accumulates.

Serious adverse events were more common on retatrutide than on placebo in both trials. Two deaths occurred in TRIUMPH-4 — one in each dose group — and both were assessed by investigators as unrelated to the study treatment. No deaths occurred in TRIUMPH-1-OA.

None of this overturns the result. But it sets the price of the benefit, and it is the reason the paper’s authors describe tolerability as “generally similar” to other drugs in this class rather than better. Anyone reading the 75.8 percent headline without the discontinuation figures is getting half the trial.

What the trials do not prove yet

The most important sentence in the paper may be the one about what the trials were not designed to test. They were not designed to show whether retatrutide slows the progression of osteoarthritis, or whether it reduces the need for total knee replacement. People who needed a knee replacement were excluded from the trials entirely. So the question every reader with bad knees actually wants answered — “will this keep me out of surgery?” — remains unanswered. Dr. Schnitzer called that the biggest unknown from the study, and the goal of future research.

There are three more limits worth stating plainly:

• Only people with overweight or obesity were studied. Whether retatrutide helps knee osteoarthritis in people who are not overweight is unknown — they were not included, and the mechanism may depend on the weight loss.
• The earliest pain measurement was at week 16. How quickly the benefit starts is not captured by these trials.
• Inflammation markers were measured only at the start and the end. Whether the drug calms inflammation inside the joint, beyond the effect of unloading it, cannot be tracked over time from this data.

These are not footnotes. They are the difference between “a drug that reduces knee pain in people with obesity” — which is what the trials proved — and “a treatment for knee osteoarthritis” in general, which is not what they proved.

What is retatrutide?

Retatrutide is Eli Lilly’s investigational once-weekly injection that activates three hormone receptors at once: GIP, GLP-1, and glucagon. The first two are the targets of tirzepatide; the third, glucagon, is the new lever, added in the hope of increasing energy expenditure on top of appetite reduction. It is the most potent weight-loss molecule Lilly has brought to Phase 3: in its Phase 2 obesity trial it produced up to 24.2 percent weight loss over 48 weeks, and in the TRIUMPH program it has now produced 20 to 29 percent depending on the trial and the analysis.

It is still investigational. It is not approved by the FDA, the EMA, or any other regulator, and it cannot be prescribed outside a clinical trial. Eli Lilly plans to submit it for FDA approval in the first quarter of 2027. The broader TRIUMPH program includes eight Phase 3 trials covering obesity, type 2 diabetes, sleep apnoea, and knee osteoarthritis, and the cardiovascular outcomes trial that will answer the long-term heart-safety question has not yet reported.

What happens next

Three things to watch from here:

• The regulatory filing. A first-quarter 2027 FDA submission is the plan Lilly has stated. Approval, if it comes, would be for obesity and related conditions; whether knee pain becomes part of the label is a separate question for regulators.
• The head-to-head trial. TRIUMPH-5, retatrutide against tirzepatide, is the next big catalyst, with primary completion estimated around November 2026. That trial answers the question doctors will actually ask: is the third receptor worth it?
• The heart question. The TRIUMPH-3 cardiovascular outcomes trial has not yet reported. For a drug that raises heart rate in a dose-dependent way — a known effect from Phase 2 — the long-term cardiovascular data will matter as much as the pain data.

What this means for readers

If you live with knee osteoarthritis and obesity, this is genuinely hopeful news — and it is not a prescription. Diet, exercise, and lifestyle change remain the first step, as the trial’s own lead author stressed: they are cheaper, they carry no drug side effects, and they keep the muscle that stabilizes the knee. The drug option, if and when it is approved, would sit alongside those foundations, not instead of them, and the decision would belong to you and your doctor — weighing a large average pain reduction against a roughly one-in-six chance of stopping treatment because of side effects.

What today changed is the quality of the evidence. Yesterday the numbers were a company announcement. Today they are a peer-reviewed publication with two independent trials pointing the same way, presented at the rheumatology field’s largest meeting. The headline got a little smaller in the translation — 75.8 percent became a post-hoc best case, and 3.7 to 4.0 points became the pre-specified result. But the result survived peer review, and the responder rates — two in three people cutting their pain in half — survived with it. That is what a verdict looks like when it holds up.

Frequently asked questions

What is TRIUMPH-4?
TRIUMPH-4 is a Phase 3 clinical trial of retatrutide in 445 adults with painful knee osteoarthritis and obesity, run over 68 weeks. Participants received once-weekly retatrutide at 9 mg or 12 mg, or a placebo. Its co-primary goals were change in knee pain and percent change in body weight. The full results were presented at ACR Convergence 2026 on November 8, 2026, and published the same day in the New England Journal of Medicine.

How much did retatrutide reduce knee pain in TRIUMPH-4?
On the trial’s pre-specified analysis, WOMAC knee pain fell 3.96 points on the 9 mg dose and 3.74 points on the 12 mg dose, against 2.12 points on placebo — a difference of 1.6 to 1.8 points, statistically significant at p < 0.001. The widely quoted 75.8 percent figure (up to 4.5 points from a baseline of 6.0) is a post-hoc calculation describing people who stayed on treatment, not the pre-specified result.

What is the WOMAC pain score?
WOMAC stands for the Western Ontario and McMaster Universities Osteoarthritis Index. Its pain subscale asks people to rate their knee pain from 0 (no pain) to 10 (worst pain). Participants in these trials started at an average of about 6.0 — moderate-to-severe pain — and rated their pain at clinic visits as well as in a daily app diary.

How many people became pain-free?
According to Eli Lilly’s announcement, more than one in eight people on retatrutide in TRIUMPH-4 ended the trial reporting no knee pain, and more than one in six in the 80-week TRIUMPH-1-OA trial. The peer-reviewed paper reports responder rates instead: pooled across both trials, 63 to 70 percent of people on retatrutide had at least half their pain gone by week 68, against 38 percent on placebo.

How much weight did people lose?
In TRIUMPH-4, body weight fell 20.0 percent on 9 mg and 23.7 percent on 12 mg, against 4.6 percent on placebo, counting everyone who was randomized. Among people who stayed on treatment, the figures were higher — 26.4 and 28.7 percent. In the 80-week TRIUMPH-1-OA trial, weight fell 17.5 to 24.8 percent on retatrutide against 4.3 percent on placebo.

What were the most common side effects?
Nausea, diarrhoea, constipation, and vomiting — the typical gut effects of this drug class. Nausea affected 38 to 43 percent of people on retatrutide against 11 percent on placebo; diarrhoea 33 to 35 percent against 13 percent; vomiting 20 to 21 percent against none on placebo. Most events were mild to moderate and happened during dose escalation. Tingling or pins-and-needles sensations (dysesthesia) occurred in 6 to 21 percent on retatrutide against 0.7 percent on placebo, and were generally mild.

How many people stopped taking retatrutide because of side effects?
In TRIUMPH-4, 12.2 percent on the 9 mg dose and 18.2 percent on the 12 mg dose stopped treatment due to adverse events, against 4.0 percent on placebo. In TRIUMPH-1-OA the figures were 2.8, 8.4, and 15.3 percent across the 4, 9, and 12 mg doses, against 6.3 percent on placebo. About half of the discontinuations in TRIUMPH-4 were due to gut events.

Is retatrutide approved? Can a doctor prescribe it?
No. Retatrutide is investigational and is not approved by the FDA, the EMA, or any other regulator. It cannot be prescribed outside an enrolled clinical trial. Eli Lilly plans to file for FDA approval in the first quarter of 2027.

How does retatrutide compare with semaglutide for knee pain?
In semaglutide’s 2024 knee osteoarthritis trial, 65.2 percent of participants had at least half their pain gone by week 68 — close to retatrutide’s 63 to 70 percent. Retatrutide’s effect size on pain was larger (0.55–0.79 vs 0.50 for semaglutide), and it produced substantially more weight loss. The trials were not head-to-head, so this is a cross-trial comparison, not a direct contest.

Will retatrutide keep me from needing a knee replacement?
That is unknown. People who needed a knee replacement were excluded from both trials, and the trials were not designed to measure whether the drug slows osteoarthritis progression or reduces the need for joint replacement. That is the biggest open question, and the one future studies need to answer.

What is TRIUMPH-5?
TRIUMPH-5 is the head-to-head Phase 3 trial of retatrutide against tirzepatide, with primary completion estimated around November 2026. It will test whether retatrutide’s third receptor — glucagon — delivers an advantage over the two-receptor drug.

Where can I read the original research?
The full paper is Schnitzer et al., “Retatrutide Once Weekly in Adults with Knee Osteoarthritis Pain and Obesity,” New England Journal of Medicine, November 8, 2026, DOI: 10.1056/NEJMoa2610676. Lilly’s announcement of the ACR presentations is on PR Newswire, November 5, 2026. Both are listed in the sources below.

Sources

1. Schnitzer TJ, Hunter DJ, Conaghan PG, et al. “Retatrutide Once Weekly in Adults with Knee Osteoarthritis Pain and Obesity.” New England Journal of Medicine, November 8, 2026. DOI: 10.1056/NEJMoa2610676. https://www.nejm.org/doi/full/10.1056/NEJMoa2610676
2. Eli Lilly and Company. “Lilly to showcase new retatrutide, Taltz (ixekizumab) and Zepbound (tirzepatide) data at ACR Convergence 2026.” PR Newswire, November 5, 2026. https://www.prnewswire.com/news-releases/lilly-to-showcase-new-retatrutide-taltz-ixekizumab-and-zepbound-tirzepatide-data-at-acr-convergence-2026-advancing-science-at-the-intersection-of-rheumatologic-conditions-and-obesity-302930037.html
3. “Experimental weight-loss drug eases painful knee osteoarthritis in two clinical trials.” MedicalXpress, November 8, 2026. https://medicalxpress.com/news/2026-11-experimental-weight-loss-drug-eases.html
4. RheumNow. “ACR 2026 – Big Pharma Brings Its Biggest Readouts to Orlando.” November 8, 2026. https://rheumnow.com/news/acr-2026-big-pharma-brings-its-biggest-readouts-orlando
5. The Inference. “Retatrutide cut knee pain up to 75.8% in Phase 3, and the fine print matters.” November 5, 2026. https://theinference.org/article/retatrutide-cut-knee-pain-up-to-75-8-in-phase-3-and-the-fine-print-matters
6. Close Concerns. “Lilly announces topline results of the phase 3 TRIUMPH-4 trial of once-weekly retatrutide in people with obesity or overweight and osteoarthritis.” December 11, 2025. https://cckb.closeconcerns.com/r/9212e4a6/pdf
7. DietGLP. “Retatrutide Knee Osteoarthritis Results: Pain Down Up to 76%.” November 5, 2026. https://www.dietglp.com/blog/retatrutide-knee-osteoarthritis/
8. Jastreboff AM, Kaplan LM, Davies MJ, et al. “Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity.” New England Journal of Medicine, September 29, 2026. DOI: 10.1056/NEJMoa2604169.
9. Bliddal H, Bays H, Czernichow S, et al. “Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis.” New England Journal of Medicine 2024;391(17):1573–1583. DOI: 10.1056/NEJMoa2403664.

This article reports on published clinical trial results for educational purposes. Retatrutide is an investigational drug that is not approved for any use. Nothing in this article is medical advice or a recommendation to use any product. Talk to your doctor about knee osteoarthritis and weight management.