Osteoarthritis, which causes stiff and painful joints, affects the knees most often.Credit: Dr. P. Marazzi/Science Photo Library

A blockbuster weight-loss drug sharply reduces pain from obesity-related knee arthritis and improves a person’s ability to engage in activities such as walking. That’s according to a clinical trial conducted in 11 countries — the first of its kind to prove that one of the new wave of anti-obesity drugs can treat arthritis. The drug, semaglutide, provided pain relief on a par with opioid drugs.

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At the end of the trial, many participants’ pain had subsided enough that they were no longer eligible for the study, says Henning Bliddal, a rheumatologist at Copenhagen University Hospital at Bispebejerg and Frederiksberg who helped to conduct the trial. “They got a therapy that was so effective that they more or less were treated out of the study,” he says.

The results are “important and could be helpful” for people with knee osteoarthritis, says Leigh Callahan, an epidemiologist at the University of North Carolina, Chapel Hill.

The findings were published today in the New England Journal of Medicine1. The trial was sponsored and designed by Novo Nordisk, which is based in Bagsværd, Denmark, and makes semaglutide, a drug sold as Ozempic for treating diabetes and Wegovy for treating obesity. Bliddal served briefly as a paid consultant to the company during trial planning.

Spreading scourge

Osteoarthritis, which causes stiff, painful joints, is among the most common conditions of ageing, and the knee is the most frequently affected joint. People who have obesity are at higher risk of developing arthritic knees because they have extra stress on their joints. Obesity also worsens symptoms, Callahan says. Pain from the condition can keep people from exercising, Bliddal says, making it extremely difficult for them to lose weight by lifestyle changes alone.

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The trial enrolled some 400 participants on five continents and randomly assigned them to receive weekly injections of either semaglutide or a placebo. They also received counselling on healthy eating and physical activity. When the trial began, participants had obesity, and their average score on a 100-point pain scale was 71 — high enough that walking was painful.

After 68 weeks of injections, participants taking semaglutide had lost much more weight than those taking the placebo. They also reported a much bigger drop on the pain scale: an average of 42 points, versus an average of 28 points for placebo recipients. These participants noticed a greater improvement in everyday functioning, such as climbing stairs, too.

The improvement probably stems in part from a decreased load on the knee stemming from weight loss, the authors write. But semaglutide also has anti-inflammatory effects, which might help to explain the pain relief.

Despite the benefits, Bliddal is concerned about the long-term outlook for those who use semaglutide to relieve knee arthritis. “Do these guys go on with semaglutide forever” to manage their pain? People who stop taking the drugs generally regain the lost weight, and the medications are expensive — a month’s supply can cost hundreds of US dollars.

Callahan emphasizes that although the results seem “very exciting”, it’s important for people to supplement anti-obesity drugs with lifestyle changes for long-term weight maintenance.

doi: https://doi.org/10.1038/d41586-024-03512-0

References

1. Bliddal, H. et al. N. Engl. J. Med. 391, 1573–1583 (2024).Article Google Scholar