CATEGORY: MOBILITY, BONES & JOINTS
A weight-loss drug took roughly four points off knee pain on a ten-point scale over about a year and a half, while a placebo took off about two. That result came from two large randomized trials of retatrutide, an experimental once-weekly injection, in adults who had both obesity and painful knee osteoarthritis, the “wear-and-tear” joint disease in which the cushioning cartilage breaks down. The findings were published in the New England Journal of Medicine and presented at a rheumatology meeting in early November.1 Pooling the two trials, 64% to 70% of people on the drug cut their pain at least in half. On placebo, 38% did.
Two trials, a year or more, nobody choosing their own shot
The companion trials were called TRIUMPH-4 and TRIUMPH-1-OA. One enrolled 445 adults and ran 68 weeks; the other enrolled 574 and ran 80. Both were double-blind and placebo-controlled, so a coin toss, not the patient or the doctor, decided who got the drug and who got the dummy injection. Everyone had knee osteoarthritis confirmed on X-ray. Most carried a lot of extra weight, and about 80% had a BMI above 35. Pain was tracked with the WOMAC scale, a standard questionnaire about how much the joint hurts and how much it limits daily movement. At the top dose, pain fell about 3.7 to 4 points against roughly 2 on placebo, a difference of 1.6 to 1.8 points that held up as statistically solid.
The weight came off, and the researchers think that’s the reason
These are striking weight figures by any measure. In the 68-week trial, people on the two higher doses lost 20.0% and 23.7% of their body weight, against 4.6% on placebo. The longer trial ran from 17.5% up to 24.8%. The investigators’ explanation is mechanical. A lighter body loads the joint less with every step, so it hurts less and moves better. They raise a possible anti-inflammatory effect too, but don’t claim it’s settled. Physical function improved alongside the pain, with about 64% of drug recipients gaining at least half their function back versus 33% on placebo. What the trials can’t tell us is whether easing pain this way slows the disease itself or puts off a knee replacement. They weren’t built to answer that, and people who already needed a new knee were left out.
The benefit came with a familiar cost
Retatrutide belongs to the same drug family as the well-known weight-loss injections, and it carried the same kinds of side effects. Nausea, diarrhea, and constipation were the most common, mostly while the dose was climbing. A skin sensation called dysesthesia, an odd tingling or prickling, reached about 21% at the highest dose versus under 1% on placebo. Serious adverse events ran around 10% to 11% on the drug against 2% on placebo in the shorter trial. And the drug was hard for some people to stay on: roughly 15% to 18% at the top dose stopped because of side effects, compared with 4% to 6% on placebo. The drug is investigational. Eli Lilly funded the trials, and it isn’t approved for this use or any other. An earlier trial of semaglutide pointed the same way in knee osteoarthritis, which makes this a second, larger piece of evidence rather than a lone result.2
Key Takeaways
- In two randomized trials, a high dose of retatrutide reduced knee pain by about 4 points on a 10-point scale over 68 to 80 weeks, versus about 2 on placebo, and 64% to 70% of people halved their pain.
- Body weight dropped 20% to nearly 25% on the higher doses, and the researchers attribute the knee relief mainly to that weight loss easing the load on the joint.
- The trials did not test whether the drug slows joint damage or prevents knee replacement, and side effects led 15% to 18% at the top dose to stop treatment.
- Retatrutide is investigational and not approved; an earlier semaglutide trial found a similar effect, so this is a second line of evidence, not a first.
References
- Schnitzer TJ, Hunter DJ, Conaghan PG, et al. Retatrutide Once Weekly in Adults with Knee Osteoarthritis Pain and Obesity. New England Journal of Medicine. 2026. link
- 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. link