407 Patient NEJM Study Tests Semaglutide for OA Patients

Authors of a new 407-patient study, sponsored by Novo Nordisk, wrote that obese patients with knee osteoarthritis (OA) and moderate-to-severe pain benefit from weekly semaglutide injections.

To be clear, the twin subjects of semaglutide and weight loss are THE hot topic today. A quick search on Google Scholar using the terms “semaglutide” and “obesity” bring up about 20,000 studies. Combining those search terms with “knee OA” and the tally drops to 800, with the #1 study being the subject of this article.

The study, a 68-week, double-blind, randomized, placebo-controlled trial at 61 sites in 11 countries, resulted in a New England Journal of Medicine (NEJM) paper titled, “Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis,” which was published in the October 30, 2024 edition.

According to the study authors, patients treated with semaglutide reported, using the Short Form-36 physical function scale, greater improvement than patients in the placebo group. How significant of a difference? The average change in the treated group was 12.0 points while the average change in the control group was about half that or 6.5 points.

The authors also report that adverse events that led to permanent discontinuation of the trial regimen occurred in 6.7% of the semaglutide treatment group and 3.0% in the placebo group. Gastrointestinal disorders were the primary reason for discontinuation.

Key attributes of the study patients were:

• Mean Body Mass Index of 40.3, and
• Mean Western Ontario and McMaster Universities Arthritis Index pain score of 70.9
• 6% of the participants were women
• Semaglutide patients recorded a mean body weight change from baseline to week 68 of −13.7%
• Placebo patients recorded a mean body weight change from baseline to week 68 of −3.2%,
• Semaglutide patients reported a Western Ontario and McMaster Universities Arthritis Index pain score change from week 1 to week 68 of −41.7 points
• Placebo patients reported a Western Ontario and McMaster Universities Arthritis Index pain score change from week 1 to week 68 of −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,” said lead study author Henning Bliddal, M.D., M.Sci. of Copenhagen University Hospital in Denmark, to OTW. “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.”