Semaglutide (Wegovy) reduced pain and improved physical function in patients with obesity and knee osteoarthritis, a randomized trial showed.
Among 407 adults, the mean change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from baseline to week 68 was -41.7 points in the semaglutide group and -27.5 points in the placebo group (P<0.001), reported Henning Bliddal, MD, of Copenhagen University Hospital at Bispebjerg and Frederiksberg, and colleagues.
Patients in the semaglutide group also had a greater improvement in their physical function score on the 36-Item Short Form Health Survey (SF-36; higher scores indicate greater well-being) compared with those in the placebo group, with a mean change of 12 points versus 6.5 points, respectively (P<0.001), they noted in the New England Journal of Medicine.
The mean change in body weight from baseline to week 68 was -13.7% with semaglutide and -3.2% with placebo (P<0.001).
"When administered to persons with obesity and KOA [knee osteoarthritis], once-weekly semaglutide can not only help reduce body weight but also improve KOA pain and functionality," Bliddal told MedPage Today.
As a 2022 report noted, "obesity remains the most important risk factor for the incidence and progression of osteoarthritis."
According to Bliddal, the researchers launched the study to answer this question: "Would a highly effective anti-obesity medication improve KOA to a clinically meaningful degree?" Other studies had tackled the question with inconsistent results, he said.
"It is intuitive that weight reduction in persons with obesity would have biomechanical benefits, such as reduced stress on the knee and other weight-bearing joints," he noted. "What is still a mystery is the degree [of anti-inflammatory effects] that GLP-1 agonist drugs may have."
In an accompanying editorial, David T. Felson, MD, MPH, of Boston University School of Medicine, wrote that "the findings confirm that substantial weight loss causes an often dramatic reduction in pain."
Obesity "markedly increases" the risk of knee osteoarthritis, he said. Extra weight increases mechanical stress on the knee, and "visceral adipose tissue secretes adipocytokines and other soluble mediators that increase pain."
Felson added that the trial's findings are similar to those from a 2023 study that examined the effects of GLP-1 receptor agonists on adults who had both type 2 diabetes and knee osteoarthritis. Those taking the drugs had fewer knee surgeries, and imaging revealed a slowing of cartilage loss.
Moving forward, Felson wrote, "it will be important to obtain data on whether semaglutide is similarly effective in persons with osteoarthritis without obesity, as well as better data on whether GLP-1 receptor agonists prevent progressive structural deterioration of the joint in osteoarthritis."
This double-blind STEP-9 study was conducted at 61 sites across 11 countries starting in October 2021. Participants with obesity (a body-mass index [BMI] of ≥30) and a clinical and radiologic diagnosis of moderate knee osteoarthritis with at least moderate pain were randomly assigned 2:1 to receive once-weekly subcutaneous semaglutide (2.4 mg) or placebo, in addition to counseling on physical activity and a reduced-calorie diet.
Mean age was 56, 81.6% were women, and 60.9% were white. Mean BMI was 40.3, and mean WOMAC pain score was 70.9. Of the participants, 48.2% had hypertension, and 30.5% had dyslipidemia.
Among the 235 participants in the semaglutide group who completed the treatment period, 89.8% were receiving the full 2.4-mg dose at the last treatment visit.
Rates of serious adverse events were similar between the intervention group and placebo group (10% vs 8.1%). Adverse events leading to discontinuation occurred in 6.7% and 3%, respectively. Gastrointestinal adverse events only led to discontinuation in the semaglutide group (2.2%).
Study limitations included a lack of imaging at follow-up and a lack of assessment of metabolic and inflammatory markers. It's not clear if the participants followed diet and exercise recommendations.
Disclosures
The study was funded by Novo Nordisk.
Bliddal reported relationships with Contura and Novo Nordisk.
Co-authors reported multiple relationships with industry, including Novo Nordisk.
Felson reported relationships with AposTherapy, the Arthritis Foundation, Boston University, University of Manchester, and the Yale School of Medicine.
Primary Source
New England Journal of Medicine
Source Reference: Bliddal H, et al "Once-weekly semaglutide in persons with obesity and knee osteoarthritis" N Engl J Med 2024; DOI: 10.1056/NEJMoa2403664.
Secondary Source
New England Journal of Medicine
Source Reference: Felson DT "Glucagon-like peptide-1 receptor agonists and osteoarthritis" N Engl J Med 2024; DOI: 10.1056/NEJMe2409972.
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