NEJM: Semaglutide Reduces Knee Osteoarthritis Pain in Obese Patients (STEP 9 Results)

In a recent publication by The New England Journal of Medicine, results from Novo Nordisk's STEP 9 phase 3 clinical trial have shown promising outcomes for semaglutide 2.4 mg in reducing body weight and alleviating knee osteoarthritis-related pain in adults with obesity. This trial focused on individuals with a clinical and radiologic diagnosis of moderate knee osteoarthritis and moderately severe pain, evaluating semaglutide against a placebo alongside lifestyle modifications.

The 68-week study was conducted with 407 participants who were randomly assigned to receive either semaglutide or a placebo. The primary endpoints were to assess the change in body weight and knee osteoarthritis-related pain, measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. The results demonstrated a significant reduction in both body weight and pain for those treated with semaglutide compared to the placebo group.

Participants with a mean starting body weight of 239.5 pounds experienced an average weight reduction of 13.7% with semaglutide, compared to a 3.2% reduction in the placebo group. Additionally, the WOMAC pain score showed a dramatic decrease from 70.9 to 41.7 for those on semaglutide, as opposed to a drop to 27.5 for the placebo group. These findings highlight semaglutide's effectiveness in addressing key symptoms of knee osteoarthritis in obese individuals.

Beyond weight reduction and pain relief, the trial also found improvements in physical function. Measured by the 36-Item Short Form Survey (SF-36v2), participants on semaglutide saw a mean increase of 12 points in their physical functioning scores, versus a 6.5-point increase in the placebo group. This indicates an enhanced ability to perform daily activities and a better overall quality of life for those taking semaglutide.

Obesity is a known risk factor for knee osteoarthritis, influencing its development and progression through increased mechanical stress on joints, metabolic factors, and related inflammation. The condition often leads to chronic pain and reduced mobility, making weight management a critical component of treatment. However, sustained weight loss and adherence to physical activity can be challenging for many individuals.

Lead author Henning Bliddal, MD, M.Sci., of The Parker Institute at Copenhagen University Hospital, emphasized the need for non-surgical, sustainable treatment options for those with obesity-related osteoarthritis. He noted that the STEP 9 trial provides rigorous evidence on the potential benefits of semaglutide for this population.

The study also focused on safety, recording serious adverse events (SAEs) and those leading to treatment discontinuation. The most common adverse events leading to discontinuation in the semaglutide group were gastrointestinal disorders and neoplasms. The incidence of SAEs was comparable between the semaglutide and placebo groups.

Anna Windle, PhD, Senior Vice President of Clinical Development at Novo Nordisk, commented on the significance of these findings, noting that they offer essential insights into the effects of semaglutide, a glucagon-like peptide-1 receptor agonist, on knee osteoarthritis outcomes in obese individuals. Novo Nordisk aims to collaborate with regulatory authorities to determine the next steps based on these promising results.

STEP 9 was a comprehensive trial involving 407 adults across 11 countries at 61 sites. Participants were randomized to receive either semaglutide 2.4 mg or a placebo for 68 weeks, followed by a seven-week off-treatment period. The primary endpoints assessed were changes in body weight and the WOMAC pain score from baseline to week 68.

While semaglutide is not currently approved for treating knee osteoarthritis, these findings provide a strong foundation for future research and potential regulatory approval. Novo Nordisk remains committed to advancing treatment options for chronic conditions like obesity and knee osteoarthritis, leveraging its extensive expertise in developing innovative medicines.