People who lost a significant amount of weight with semaglutide saw major improvements in osteoarthritis knee pain, research published Wednesday in the New England Journal of Medicine finds.
In the phase 3 clinical trial, people with osteoarthritis who dieted, exercised and took semaglutide — the blockbuster drug sold by Novo Nordisk as Ozempic and Wegovy — lost more weight and reported a greater reduction in knee pain than those who lost weight with just diet and exercise.
Osteoarthritis happens when cartilage around joints breaks down. The leading cause, experts say, is obesity.
“Within a joint, you have cartilage that coats and caps the bones so they glide together smoothly,” said Dr. Daniel Wiznia, co-director of the Yale Medicine Avascular Necrosis & Osteonecrosis Program. “Cartilage is not designed for high stress loads that it will see with obesity.”
The new study, which was funded by Novo Nordisk, included about 400 patients with knee osteoarthritis, with an average age of 56, in 11 countries. About 80% of the people in the study were women, who experience osteoarthritis at higher rates than men. The participants reported their pain to be about 71 out of 100, on average, which is “pretty severe pain,” said lead study author Dr. Henning Bliddal, a professor of rheumatology at the University of Copenhagen in Denmark.
All the participants were overweight, and almost all had body mass indexes over 30, which is the threshold for obesity. About 40% had BMIs over 40, considered severe obesity.
They got either a weekly injection of semaglutide or a placebo for 68 weeks. Everyone also got guidance on how to stick to reduced-calorie diets and incorporate exercise into their routines.
At the end of the trial, the participants who took semaglutide lost an average of about 14% of their body weight — roughly 33 pounds — compared to about 3% in the placebo group. People who took semaglutide also reported about a 42-point drop on the pain scale, compared to a drop of 27.5 in the control group.
“This is a very big effect on pain, bigger than the other nonsurgical treatments we have,” said Dr. David Felson, a professor of medicine at the Boston University Chobanian & Avedisian School of Medicine.
That’s likely due to the fact that, pound for pound, extra weight has an outsize effect on joints.
“Every extra pound you have over a healthy BMI is an extra 5 to 8 pounds of pressure on your knees,” Wiznia said. “If you lose that weight, that will be a significant amount of pressure off of your knees.”
Previous research has found that bariatric surgery, which can also lead to significant weight loss, improved knee pain and function in people with osteoarthritis.
“Any sort of dramatic weight loss will relieve pain,” Bliddal said.
In another study led by Bliddal, people with knee osteoarthritis were given an older weight loss drug, liraglutide. The average BMI in that study was about 32, lower than the average in the new study. In that study, people who used diet and exercise in addition to liraglutide lost about 6 pounds and didn’t report much improvement in their pain symptoms.
Although some animal studies have suggested that semaglutide may have an anti-inflammatory effect outside of weight loss, the improvement in pain is likely due to weight loss rather than any anti-inflammatory effects of the medication, Felson said.
Wiznia said that for people who are in need of a knee replacement, semaglutide may help get them to a safer weight before surgery, or even manage pain enough to delay surgery a few more years or negate the need for it all together. The drug, however, is still in shortage, according to the Food and Drug Administration, and is unaffordable for many.
However, the results of the study may not apply to everyone. Most of the people in the study had BMIs over 35, and nearly half had BMIs of over 40.
“It’s not clear that this would be as effective in people who weren’t so obese,” Felson said, noting that people with lower BMIs may not see as extreme results.
