Can Ozempic and Wegovy help reduce knee osteoarthritis-related pain?

This new study featured the results from the STEP 9 phase 3 clinical trial conducted by healthcare company Novo Nordisk aimed at evaluating the efficacy of semaglutide versus placebo as an additional to lifestyle modifications — such as eating a reduced-calorie diet and exercising — in lowering weight and knee osteoarthritis-related pain in patients with obesity.

Researchers recruited 407 participants with an average age of 56 and body-mass index (BMI) of 40.3 for the study, who received either a 2.4 mg dose of semaglutide once a week or a placebo for 68 weeks.

At 68 weeks, researchers found that participants taking semaglutide experienced a mean decline in their body weight by 13.7%, compared to a 3.2% decrease in those taking the placebo.

Researchers also evaluated study participants’ Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores during this study. WOMAC is a patient-reported questionnaire that helps rank pain on a scale of zero to 100, with higher numbers indicating more pain.

Scientists discovered that those taking semaglutide experienced a mean decrease in their WOMAC pain score of 41.7 points from 70.9 at the start of the study, compared to those taking the placebo whose WOMAC scores only decreased by 27.5 points.

“Obesity-related knee osteoarthritis is a progressive condition that can lead to pain and stiffness of the knee and impair critical daily functions such as walking or moving around,” Henning Bliddal, MD, MSci, clinical professor in the Department of Clinical Medicine and director of the Parker Institute at Copenhagen University Hospital in Denmark and lead author of this study says in a press release.

“The risk of developing the condition is more than four times higher in people with obesity. Weight reduction along with physical activity is often a recommended approach to managing painful symptoms, but adherence can be challenging. There is a significant need for non-surgical and sustainable treatment options for those living with obesity-related osteoarthritis. The STEP 9 trial aimed to provide rigorous evidence as to how semaglutide may help these people,” Bliddal says.

After reviewing this study, Mir Ali, MD, a board certified general surgeon, bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, told Medical News Today that its findings were in line with what doctors have seen with any kind of weight loss.

“As a patient loses weight, all of their medical conditions improve, including pain from osteoarthritis. They’re taking pressure off of those joints, so it improves their discomfort and we see that with our surgical weight loss patients as well.”
— Mir Ali, MD

“That’s a big factor for a lot of people because the more discomfort they have in their joints, the less active they are. And the less active they are, the easier it is to gain weight. So if you can find ways to reduce pain and inflammation in the joints to allow them to be more active, then they can be more proactive about exercise and other ways to improve their health and lose weight,” Ali explained.

Ali said he would be interested in seeing if researchers can eventually show that semaglutide improves inflammation independent of weight loss.

“That would be a tough study to design, but that would be helpful to show that there’s some additional effect, not just the weight loss,” he added.

MNT also spoke with Bert Mandelbaum, MD, sports medicine specialist and orthopedic surgeon at Cedars-Sinai Kerlan-Jobe Institute and Co-Director of the Regenerative Orthobiologic Center at Cedars-Sinai Medical Center in Los Angeles, about this study.

“Certainly we have always known that obesity is a risk factor for not only the onset of osteoarthritis, but the progression of it — there is no question about that. When you have a study like this that shows that there’s two things that are happening at one time. One is that obviously their patients are losing weight, so there’s a physical and mechanical aspect, but also there’s something about semaglutide that also has an anti-inflammatory (effect).”
— Bert Mandelbaum, MD

“It’s not proven in this study, but there have been other studies that show that (semaglutide) reduces cardiovascular risks. And the mechanisms of that are that it is functionally an anti-inflammatory as well. It has another effect, creating a decreased inflammation that affects blood vessels in and of themselves, as well as other catabolic mediators such as the interleukins and TNF (tumor necrosis factor), and other metalloproteases seem to be inhibited as part of its inhibitory inflammatory effect,” Mandelbaum said.

Mandelbaum said doctors are looking for help in reducing pain from osteoarthritis, whether it’s related to obesity or not.

“Obesity is just a negative factor that worsens the challenge for us. We’re trying to reduce the amount of what we call catabolism and create an anabolic environment for the joints,” he explained.

“I think if researchers have found that we could reduce cardiovascular disease with these medicines, we can reduce the pain from osteoarthritis,” Mandelbaum continued.

“At the end of the day, the orthobiologic family, we have to look at other things that can make a difference, along with taking Wegovy or any of the other GLP-1s. So I think it’s an interesting study, but (it) really portends us to really think about what our next steps are so we can get into more adjuvant approaches, in addition to this, at the same time,” he added.