The blockbuster drug semaglutide, sold as Ozempic for diabetes and as Wegovy for weight loss, now has a new proven benefit: It markedly soothed knee pain in people who are obese and have moderate to severe osteoarthritis, according to a large study.
The effect was so pronounced that some arthritis experts not involved with the clinical trial were taken aback.
“The magnitude of the improvement is of a scope we haven’t seen before with a drug,” said Dr. Bob Carter, deputy director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. “They had an almost 50 percent reduction in their knee pain. That’s huge.”
Dr. David T. Felson, an arthritis expert and professor of medicine at Boston University School of Medicine, said the study “changes the landscape,” adding that the pain reduction is greater than anything that can be achieved short of knee replacement surgery.
The results were published Wednesday in the New England Journal of Medicine.
Knee osteoarthritis affects nearly one in five Americans over the age of 45. Those with obesity are especially likely to develop it because their weight puts more stress on the knee and because obesity is associated with inflammation, which contributes to deterioration of cartilage.
There are no good medical treatments. Doctors can suggest patients take over-the-counter pain relievers like acetaminophen or ibuprofen. But long-term use of those medications can damage vital organs.
When the pain gets bad enough, many turn to knee replacement surgery.
“The good news is that surgery works for most people,” Dr. Carter said. “The bad news is that it is hugely expensive,” draining money from Medicare.
“We desperately need an effective way to treat knee pain,” he added.
In the 68-week study by Novo Nordisk, the maker of semaglutide, 407 people with obesity and knee osteoarthritis were randomly assigned to receive semaglutide in the form of Wegovy or a placebo. All patients also received exercise counseling and a reduced calorie diet.
The participants were mostly women. They had an average age of 56 and an average body mass index of 40.3, placing them firmly in the obesity category. They had to have knee pain and meet additional criteria for knee osteoarthritis like stiffness in the morning or knees that creaked or clicked when they walked. Their average pain on a 100-point scale was 70.9 at the start of the study.
“They were really in pain,” said Dr. Henning Bliddal, the principal investigator for the study and a rheumatologist at Copenhagen University Hospital. “They can’t exercise. You are trapped with knees like this.”
As expected, those who received semaglutide lost a significant amount of weight — an average of 13.7 percent of their starting weight — while those who got the placebo lost 3.2 percent of their starting weight.
The study’s primary outcome was a change in a standard measure called WOMAC, which assesses pain, physical functioning and stiffness on a 100-point scale. Those who got semaglutide had an average reduction of 41.7 points, while those who got the placebo had a reduction of 27.5 points.
Dr. Carter said that placebo participants often reported some degree of pain relief in studies. But, he added, the 41.7 point drop in the pain score of semaglutide participants “is huge.”
“To be frank, this is what we had hoped for,” Dr. Bliddal said. “But it even exceeded our expectations.”
Semaglutide controls blood sugar, curbs food cravings and reduces appetite. But it also has other effects — it reduces the risk of having a heart attack, stroke or cardiovascular death in people with heart disease, and it reduces the risk of kidney complications, heart issues and death in people with kidney disease.
Doctors and many patients have high hopes that the drugs can do much more, and they cite observational studies leading to clinical trials now underway testing the drugs for treating addiction, Parkinson’s disease, Alzheimer’s disease, depression and schizophrenia.
One potential reason for some of these effects — and a possible reason semaglutide helped people with knee osteoarthritis — is that the drug seems to quell inflammation, a central factor in a variety of diseases, including obesity and osteoarthritis.
Until fairly recently, investigators thought knee osteoarthritis was a mechanical problem. Cartilage wears down. The natural cushioning around the knee joint erodes. And heavier people are more at risk because their greater weight puts more strain on their joints.
But the more they studied arthritis, the more researchers discovered that mechanical damage may not be the only factor.
“The pain seemed out of proportion” to the damage actually observed in patients, said Dr. Felson, who wrote an editorial accompanying the study.
And the pain is not just because cartilage that lies over the bone gets worn down, Dr. Carter added.
In arthritis, the lining of a thin rim of cartilage that lies over the bone becomes inflamed and sends pain signals to the spinal cord.
The bone itself also contributes to the pain. With arthritis the knee bone changes, Dr. Carter said. Pores open in the bones that didn’t use to be there, and nerves from the bone grow into the base of the cartilage.
Now, with the new study, it looks as if there is a way to treat both the mechanical problem caused by excess weight and the other factors with just one very expensive drug.
But Dr. Carter is hopeful. If it could be learned what exactly semaglutide is doing inside the joint, perhaps researchers could develop drugs that do the same thing and cost less.
“We never really understood where the pain was coming from,” he said. Now, perhaps, there is a handle to figure it out.
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