Once-Weekly Semaglutide Reduces Knee Osteoarthritis Pain, Body Weight in Patients with Obesity, Suggesting Potential to Lower NSAID Use

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Results from the STEP 9 trial (NCT05064735) show that patients with obesity administered once-weekly semaglutide experienced a significant reduction in knee osteoarthritis pain and body weight with improved physical function.^1,2 These results, published by The New England Journal of Medicine, suggest that the impact of semaglutide on weight reduction may help patients avoid the use of non-steroidal anti-inflammatory drugs and other pain medications, such as opioids, according to the study authors.

“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. “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.”¹

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist (RA), was initially approved in June 2021 for chronic weight management in those with obesity or overweight and at least one weight-related condition, including high blood pressure, type 2 diabetes, or high cholesterol, in addition to diet and increased exercise.³ Semaglutide has been approved by the FDA 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, in addition to a reduced calorie diet and increased physical activity.⁴

The 68-week, double-blind, randomized, placebo-controlled trial was conducted at 61 sites across 11 countries. Investigators enrolled 407 participants with a clinical and radiologic diagnosis of moderate knee osteoarthritis with at least moderate pain, a mean age of 56 years, mean BMI of 40.3, and a mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score of 70.9. A total of 81.6% of participants enrolled in the trial were women. Participants were randomly assigned in a 2:1 ratio to either once-weekly subcutaneous semaglutide 2.4 mg or placebo, along with counseling for physical activity and a reduced-calorie diet.

From baseline to week 68, patients in the semaglutide cohort achieved a mean change in body weight of −13.7% compared to −3.2% in the placebo cohort (P<0.001). 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). The semaglutide cohort also showed a greater improvement in the 36-Item Short Form Health Survey physical-function score compared with the placebo cohort (mean change, 12.0 points vs. 6.5 points; P<0.001).

In terms of safety, 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.

“Treatment with semaglutide resulted in greater improvements than placebo across all pain-related end points, a finding that is in line with those from an observational study involving adults with knee osteoarthritis and type 2 diabetes, in which greater reductions in WOMAC total and pain scores were seen among participants who received GLP-1 receptor agonists than among those who did not receive these agents (mean BMI at baseline, 25),” the study authors wrote. “In contrast, a trial of the GLP-1 receptor agonist liraglutide (administered subcutaneously once daily at a dose of 3.0 mg) that involved participants with overweight or obesity and knee osteoarthritis showed no significant differences in pain as compared with placebo (according to the Knee Injury and Osteoarthritis Outcome Score).”¹

References

1. Bliddal, H., et al. Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis. Published October 30, 2024. N Engl J Med 2024;391:1573-1583. DOI:10.1056/NEJMoa2403664. Vol. 391 No. 17

2. Research Study Looking at How Well Semaglutide Works in People Suffering From Obesity and Knee Osteoarthritis. ClinicalTrials.gov. Updated August 13, 2024. Accessed November 6, 2024. https://clinicaltrials.gov/study/NCT05064735

3. FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014. FDA. News release. June 4, 2021. Accessed November 6, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014

4. Wegovy® receives FDA approval for cardiovascular risk reduction in adults with known heart disease and overweight or obesity. Novo Nordisk. News release. March 8, 2024. Accessed November 6. https://www.novonordisk-us.com/media/news-archive/news-details.html?id=167031