DENMARK – Novo Nordisk’s STEP 9 trial, published in The New England Journal of Medicine, has revealed that Wegovy (semaglutide) significantly reduces body weight and knee pain while improving function in adults with obesity-related knee osteoarthritis.
The trial successfully met both its primary and secondary endpoints, demonstrating significant reductions in body weight and knee pain, along with improved physical function among adults affected by these conditions.
Patients suffering from obesity are more than four times as likely to develop knee osteoarthritis, often facing limited non-surgical treatment options.
As Novo Nordisk plans to engage with regulatory authorities regarding potential label expansion, the results may set the stage for broader applications of semaglutide in treating joint issues.
Trial design and results
The 68-week Phase III trial included 407 adults with moderate knee osteoarthritis and obesity.
Participants were randomly assigned to receive weekly doses of Wegovy (2.4 mg) or a placebo, complemented by lifestyle changes. The trial included 16 weeks of dose escalation to mitigate gastrointestinal side effects.
By the end of the trial, those on Wegovy experienced an average body weight reduction of 13.7%, compared to just 3.2% in the placebo group.
Furthermore, the Wegovy group showed a significant improvement of 41.7 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score, compared to 27.5 points for those receiving a placebo.
In terms of physical function, participants on Wegovy reported an average increase of 12.0 points on the 36-Item Short Form Survey, while the placebo group saw an increase of only 6.5 points.
Safety and adverse events
While Wegovy showed promising efficacy, safety outcomes were comparable to those of the placebo. The incidence of serious adverse events stood at 10% in the Wegovy group versus 8.1% in the placebo group.
However, discontinuations due to adverse events were higher among Wegovy users (6.7%) compared to placebo recipients (3%).
Despite these side effects, the potential benefits for knee osteoarthritis make Wegovy a valuable consideration for patients seeking alternatives to surgery or conventional pain management.
Previous approvals and broader implications
Wegovy gained U.S. approval in 2021 for chronic weight management in adults, later extending its indication to include children aged 12 and older.
Earlier this year, the FDA also authorized the GLP-1 medication for reducing the risk of major adverse cardiovascular events.
The current study was part of Novo Nordisk’s exploration into whether knee osteoarthritis could be added to the expanding list of conditions that GLP-1 receptor agonists can effectively treat, potentially increasing insurance coverage options for patients.
With the positive outcomes of the STEP 9 trial, Novo Nordisk intends to engage with regulatory authorities for potential label expansion, further broadening Wegovy’s indications to include knee osteoarthritis.
Obesity is a major contributor to knee osteoarthritis, with individuals affected by obesity being over four times more likely to develop this debilitating joint condition than those with a healthy body weight.
According to Dr. Henning Bliddal, lead author and professor of rheumatology at the University of Copenhagen, “The STEP 9 trial aimed to provide rigorous evidence as to how Wegovy could help this population.”
Expert insights on weight loss and joint health
Dr. David Felson, a professor of medicine at Boston University, emphasized the study’s implications, stating, “This is a very big effect on pain, bigger than the other nonsurgical treatments we have.”
Felson noted that excess weight significantly impacts joint health, explaining, “Every extra pound you have over a healthy BMI exerts an additional 5 to 8 pounds of pressure on your knees.”
Wiznia, another expert in the field, highlighted the benefits of weight loss, saying, “If you lose that weight, that will be a significant amount of pressure off of your knees.”
While previous research has shown that significant weight loss can alleviate knee pain, the current findings suggest Wegovy may help patients achieve these outcomes non-surgically.
Though the study’s results are promising, they primarily apply to a specific demographic: participants predominantly had a BMI over 30, with many exceeding 40, which is classified as severe obesity.
The study marks a hopeful step toward effective, accessible treatments for individuals with obesity-related osteoarthritis, offering not only relief but an improved quality of life.
Dr. Felson notes, “For those in need of joint relief, Wegovy may offer an opportunity to manage symptoms enough to delay surgery or possibly avoid it altogether.”
