https://immattersacp.org/weekly/archives/2024/11/05/2.htm

Semaglutide-induced weight loss reduced knee osteoarthritis pain, industry trial finds

In patients with obesity and osteoarthritis randomly assigned to semaglutide or placebo, those in the former group had a significantly greater mean decrease in body weight and pain over 68 weeks, although trial withdrawal due to adverse events was also higher in those taking semaglutide.


Once-weekly injectable semaglutide resulted in significantly greater reductions in body weight and pain than placebo in patients with obesity and knee osteoarthritis with moderate to severe pain, an industry-supported study found.

Researchers conducted a 68-week, double-blind, randomized, placebo-controlled trial at 61 sites in 11 countries in patients with a body mass index (BMI) of 30 m/kg2 or above and clinical and radiologic evidence of moderate knee osteoarthritis with at least moderate pain. Patients were randomized to either weekly semaglutide, 2.4 mg, or placebo, in addition to counseling on physical activity and a reduced-calorie diet. The trial was sponsored by semaglutide's manufacturer, Novo Nordisk. Results were published Oct. 30 by the New England Journal of Medicine.

The primary end points were percentage change in body weight and change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score (range, 0 to 100, with higher scores reflecting worse outcomes) from baseline to week 68. Secondary end points included the physical function score on version 2 of the 36-Item Short-Form Health Survey (SF-36) (range, 0 to 100, with higher scores indicating greater well-being).

Of 407 participants, 271 were assigned to receive semaglutide and 136 were assigned to receive placebo. Overall, 81.6% were women, mean age was 56 years, mean baseline BMI was 40.3 m/kg2, and mean WOMAC pain score was 70.9. The mean change in body weight from baseline to week 68 was −13.7% with semaglutide versus −3.2% with placebo (P<0.001), while the mean change in WOMAC pain score was −41.7 points versus −27.5 points, respectively (P<0.001). Patients taking semaglutide had more improvement in the SF-36 physical function score than those in the placebo group (mean change, 12.0 points vs. 6.5 points; P<0.001). Adverse events, most commonly GI-related, led to trial withdrawal in 6.7% of the semaglutide group versus 3.0% in the placebo group.

The study authors noted that they did not perform follow-up imaging or assess metabolic and inflammatory markers and adherence to recommendations about diet and physical activity, among other limitations. Subgroup analyses indicated a benefit of semaglutide with respect to pain regardless of BMI at baseline, but mean BMI and pain scores at baseline were higher than in previous studies of persons with knee osteoarthritis, the authors said.

An accompanying editorial noted that “if the effects shown in this trial are mediated by factors other than weight loss alone, new therapeutic avenues may be available,” calling for “data on whether semaglutide is similarly effective in persons with osteoarthritis without obesity, as well as better data on whether [glucagon-like peptide-1] receptor agonists prevent progressive structural deterioration of the joint in osteoarthritis.”