A recent study published in The New England Journal of Medicine reveals that once-weekly semaglutide significantly reduces knee osteoarthritis pain and body weight while improving physical function in patients with obesity. The STEP 9 trial (NCT05064735) suggests that semaglutide's effect on weight reduction could help patients avoid non-steroidal anti-inflammatory drugs (NSAIDs) and other pain medications.
The 68-week, double-blind, randomized, placebo-controlled trial was conducted across 61 sites in 11 countries. It involved 407 participants with a clinical and radiologic diagnosis of moderate knee osteoarthritis with at least moderate pain. The mean age of participants was 56 years, with a mean BMI of 40.3 and a mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score of 70.9. The study population was 81.6% women. Participants were randomized in a 2:1 ratio to either once-weekly subcutaneous semaglutide 2.4 mg or placebo, alongside counseling for physical activity and a reduced-calorie diet.
Significant Pain and Weight Reduction
From baseline to week 68, the semaglutide cohort achieved a mean change in body weight of -13.7% compared to -3.2% in the placebo cohort (P<0.001). The mean change in WOMAC pain score at week 68 was -41.7 points in the semaglutide cohort compared with -27.5 points in the placebo cohort (P<0.001). Furthermore, the semaglutide cohort showed greater improvement in the 36-Item Short Form Health Survey physical-function score compared to the placebo cohort (mean change, 12.0 points vs. 6.5 points; P<0.001).
Safety Profile
Serious adverse events (AEs) were similar across both cohorts. AEs causing permanent discontinuation were reported by 6.7% of patients in the semaglutide cohort compared with 3.0% in the placebo cohort. The most common AEs causing discontinuation were gastrointestinal disorders.
Expert Commentary
"The STEP 9 trial, which involved persons with obesity and moderate-to-severe pain due to knee osteoarthritis, showed that semaglutide was superior to placebo in reducing pain related to knee osteoarthritis as well as body weight and was associated with improved physical function," the study authors wrote. They added, "Although previous studies have indicated a benefit of weight reduction with respect to symptoms, this randomized trial used full blinding of the participants to the trial-group assignment and also showed larger effects. Weight reductions and safety outcomes with semaglutide were consistent with those reported in previous STEP trials."
Semaglutide Background
Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist (RA), was initially approved in June 2021 for chronic weight management in individuals with obesity or overweight and at least one weight-related condition, such as high blood pressure, type 2 diabetes, or high cholesterol, in addition to diet and increased exercise. Semaglutide is available in both long-acting injectable (Wegovy and Ozempic) and daily oral tablet (Rybelsus) formulations. In March 2024, Wegovy (semaglutide) was approved by the FDA to reduce the risk of major adverse cardiovascular events in adults with known heart disease and with obesity or overweight, alongside a reduced-calorie diet and increased physical activity.
