You asked about retatrutide and knee osteoarthritis pain results, so here is the short answer. In two large late-stage trials, adults with painful knee osteoarthritis and obesity who took retatrutide reported more pain relief than people given placebo (an inactive dummy treatment), and they also lost more weight.
Retatrutide is still investigational. As of November 9, 2026, it is not FDA approved for knee osteoarthritis or for any other use, and researchers cannot yet say how much of the pain relief comes from weight loss itself.
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What did the retatrutide knee osteoarthritis studies measure?
The results come from two phase 3 trials, which are the large final-stage studies a drug goes through before it can be submitted for approval. They were published in the New England Journal of Medicine as NEJM article on retatrutide knee pain, titled “Retatrutide Once Weekly in Adults with Knee Osteoarthritis Pain and Obesity.” Eli Lilly funded the work.
TRIUMPH-4 enrolled 445 participants and followed them to week 68. TRIUMPH-1-OA enrolled 574 participants and followed them to week 80. Everyone was an adult without diabetes, had painful knee osteoarthritis, and had a body-mass index (BMI) of at least 27. Participants were randomly assigned to retatrutide, given once a week by injection under the skin, or to placebo. The trial registration is listed as ClinicalTrials.gov registration NCT05929066.
The main pain measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, scored from 0 to 10. Higher numbers mean worse pain. The trial design is described in a TRIUMPH trial design paper indexed by PubMed.
How big were the pain and weight results?
The pain numbers use what the paper calls a hybrid-treatment estimand, which handles events suggesting treatment failure with a hypothetical strategy and uses a treatment-policy strategy elsewhere. The paper also reports an intention-to-treat (ITT) estimand, whose differences were smaller. Both sets of differences were statistically significant.
TRIUMPH-4, at week 68
| Group | WOMAC pain change | Difference vs placebo | ITT difference | Body weight change |
|---|---|---|---|---|
| Retatrutide 9 mg | -3.96 | -1.83 | -1.70 | -20.0% |
| Retatrutide 12 mg | -3.74 | -1.61 | -1.38 | -23.7% |
| Placebo | -2.12 | Reference | Reference | -4.6% |
The ITT differences were P < 0.001 for both doses.
TRIUMPH-1-OA, at week 80
| Group | WOMAC pain change | Difference vs placebo | ITT difference |
|---|---|---|---|
| Retatrutide 4 mg | -3.22 | -1.35 | -0.96 |
| Retatrutide 9 mg | -3.48 | -1.61 | -1.41 |
| Retatrutide 12 mg | -3.64 | -1.77 | -1.64 |
| Placebo | -1.87 | Reference | Reference |
The ITT differences were Pā¤0.005 for all comparisons.
In plain terms, a difference of -1.83 means the 9 mg group’s pain score dropped 1.83 points more than the placebo group’s on the 0-to-10 scale. These are group averages from the trials, not a prediction for any one person. The paper’s own conclusion is that retatrutide produced significantly greater reductions in both WOMAC pain and body weight than placebo in people with painful knee osteoarthritis and obesity.
Is retatrutide approved for knee osteoarthritis?
No. Retatrutide is an investigational once-weekly injection that acts on three hormone receptors: GIP, GLP-1 and glucagon. Investigational means it is still being tested and has not been approved. It is not FDA approved. The paper’s background describes it as possibly useful for painful knee osteoarthritis in people with obesity, and that is the stage the research is at.
Talk with your prescriber or clinician about whether any of this applies to your knee pain, your weight or your medicines. This is information, not medical advice.
What are the side effects?
In both trials, serious adverse events (serious side effects) were more common with retatrutide than with placebo. The most common side effects were gastrointestinal, meaning stomach and digestive symptoms. The table below sums up what has been reported so far.
| Side effect | What the trials reported |
|---|---|
| Serious adverse events | More common with retatrutide than placebo, in both trials |
| Gastrointestinal events (stomach and digestive) | The most common adverse events in both trials |
| Dysesthesia (an abnormal, often unpleasant skin sensation) | Eli Lilly’s December 2025 topline results, as reported by MPR and Rheumatology Advisor: 8.8% on 9 mg, 20.9% on 12 mg, and 0.7% on placebo. Mostly mild. |
Tell your prescriber about any new tingling, burning or numbness, and about stomach symptoms that do not settle.
Does the knee pain improve because of weight loss, the drug itself, or both?
Everyone in these trials had obesity, and the retatrutide groups lost much more weight than the placebo groups. Researchers do not yet know whether the pain relief comes from weight loss, from the drug acting directly, or from both. These trials cannot yet tell those three apart.
Body weight is linked to knee osteoarthritis in general. The NIAMS osteoarthritis overview lists being overweight or obese among the factors that can make osteoarthritis more likely.
What is knee osteoarthritis, and is it serious?
Osteoarthritis is a degenerative joint disease, in which the tissues in the joint break down over time. It is the most common type of arthritis, and it is more common in older people, according to the NIAMS osteoarthritis overview. Anyone can get it.
It can be serious for some people. The NIAMS overview says osteoarthritis affects each person differently: for some it is relatively mild and does not affect daily activities, and for others it causes significant pain and disability. Damage usually develops gradually over years, although it could worsen quickly in some people.
In the knee, typical symptoms include pain when using the joint, stiffness lasting less than 30 minutes in the morning or after rest, swelling, and a grinding or scraping noise when you move. Over time, muscle and ligament weakness can cause the knee to buckle.
What causes knee osteoarthritis?
Researchers do not know what triggers the breakdown of joint tissue. The NIAMS overview says it is not simple wear and tear. Certain factors make it more likely, including:
- Aging
- Being overweight or obese
- A history of injury or surgery to a joint
- Overuse from repetitive movements of the joint
- Joints that do not form correctly
- A family history of osteoarthritis
Younger people can develop it too, usually after a joint injury, an abnormal joint structure, or a genetic defect in joint cartilage.
Can knee osteoarthritis be reversed?
The retatrutide trials measured knee pain and body weight. They tell you about symptoms and weight, not about whether the joint tissue repairs itself. For what else people use for knee pain, read knee osteoarthritis treatment options, which covers the evidence and side effects of the other options.
What did TODAY report?
TODAY (NBC) reported on November 9, 2026, in its TODAY video that a recent poll found about 1 in 8 American adults say they currently take GLP-1 weight-loss drugs. Its video description also says a New England Journal of Medicine study finds retatrutide, still in trials, could give significant relief for painful knee arthritis. That NEJM study is the one covered above. The paper reports measured results from two trials, and the video offers a short summary of them.
What should you ask at a visit?
If you want to raise retatrutide with your prescriber, these questions help:
- Is retatrutide an option for my knee pain, given that it is not FDA approved?
- If it were an option, how would we track my knee pain and weight?
- Which side effects should I report right away, including tingling, burning, numbness and stomach symptoms?
- Could any of my current medicines matter here?
Bring your list of medicines. The guide to your medication list for a pain-care visit explains what to write down. Each day, rate your knee pain from 0 to 10, the same scale the WOMAC pain score uses, so you have something specific to bring. If your plan changes, the questions in when a pain-care plan changes can help you follow up.
By the Pain Care Questions Team
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