People with knee arthritis lost about a quarter of their body weight on a new weekly injection, and two-thirds had their knee pain cut in half
Knee osteoarthritis makes walking and climbing stairs painful for millions of people, and extra weight adds load to the joint with every step. Researchers at Northwestern University led two phase 3 trials of retatrutide, an experimental weekly weight-loss injection from Eli Lilly, in more than 1,000 adults with painful knee osteoarthritis and excess weight. Participants were randomly assigned to different doses of the drug or a placebo for about 68 weeks. The trials measured weight loss and knee pain.
People on the highest dose lost about a quarter of their body weight on average, and some lost 100 pounds or more. About two-thirds of participants on retatrutide had their knee pain cut by at least half.
They also had lower blood pressure, better blood fat levels and less inflammation throughout the body.
“The findings are really saying for people who are overweight and have OA, if you lose a significant amount of weight with this treatment, there is a good chance that you’re going to get a meaningful reduction in your knee pain,” said corresponding author Thomas Schnitzer of Northwestern University Feinberg School of Medicine.
Retatrutide works differently from the weight-loss drugs already on the market. Semaglutide, sold as Ozempic and Wegovy, acts on one hormone receptor, and tirzepatide, sold as Mounjaro and Zepbound, on two. Retatrutide acts on three, and in its phase 2 trial, published in 2023, people on the highest dose lost about 24% of their body weight in 48 weeks. Current drugs typically produce weight loss of 10% to 20%.
The two new trials were TRIUMPH-4, with 445 participants who received 9 mg or 12 mg of retatrutide or a placebo, and TRIUMPH-1-OA, with 574 participants from a larger obesity trial who received 4 mg, 9 mg or 12 mg or a placebo. Everyone also got lifestyle counseling. Both were published in the New England Journal of Medicine and presented at the American College of Rheumatology meeting.
The second finding is what the trials could not answer. People who already needed a knee replacement were excluded, and the trials did not show whether the drug slows the joint damage itself. “The biggest unknown,” Schnitzer said, is whether retatrutide slows osteoarthritis enough to reduce the need for total joint replacement. The researchers also want to test whether it helps knee pain in people who are not overweight.
The drug is not approved anywhere yet. Versions sold online as research chemicals are not the same as the tested product, and people who took them reported unexpected side effects, as an AI analysis of 150,000 Reddit posts recently found. For people living with knee pain, the practical message for now is that weight loss by any safe route tends to ease the load on the joint. Chronic pain is shaped by more than the joint itself, as research on how the brain processes back pain shows.
There are limits to what this shows. Retatrutide was developed by Eli Lilly, which will seek its approval, so the trials’ funding and conflict statements are worth checking. The press materials do not detail side effects, which for this class of drugs commonly include nausea and other digestive problems, and the main trial lasted 68 weeks, so long-term effects on the joint are unknown.
Source
Schnitzer TJ, et al. “Retatrutide Once Weekly in Adults with Knee Osteoarthritis Pain and Obesity.” New England Journal of Medicine, 2026.
DOI: ADD-DOI-HERE
Also cited
Jastreboff AM, Kaplan LM, Frías JP, et al. “Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 Trial.” New England Journal of Medicine, 2023.
DOI: 10.1056/NEJMoa2301972
