medwireNews: Treatment with the glucagon-like peptide (GLP)-1 receptor agonist semaglutide may significantly reduce both bodyweight and knee pain in nondiabetic individuals who have obesity and knee osteoarthritis, suggest findings from the STEP 9 trial.
David Felson (Boston University School of Medicine, Massachusetts, USA) says in a related editorial in The New England Journal of Medicine: “The findings confirm that substantial weight loss causes an often dramatic reduction in pain,” adding that the research may “open the door to more effective treatments than have heretofore been available.”
Investigator Henning Bliddal (Copenhagen University Hospital, Denmark) and team enrolled 407 nondiabetic adults (mean age 56 years, 81.6% women) into their multicenter trial. The patients had a BMI of 30 kg/m2 or above (mean 40.3 kg/m2), and a clinical and radiologic diagnosis of moderate knee osteoarthritis with moderate-to-severe pain, according to American College of Rheumatology criteria.
The participants were randomly assigned to receive weekly subcutaneous injections of either semaglutide or placebo. The semaglutide group started at an initial dose of 0.24 mg per week, gradually increasing to a target dose of 2.4 mg by week 16 to help mitigate gastrointestinal side effects. Both groups received counseling on the importance of a reduced-calorie diet and increased physical activity to aid in weight management and alleviate osteoarthritis symptoms.
After 68 weeks of treatment, the 271 individuals treated with semaglutide experienced a mean 13.7% reduction in bodyweight, from a pretreatment overall average of 108.6 kg. This weight loss was a significant 10.5 percentage points greater than the 3.2% reduction observed in the placebo group.
Semaglutide recipients also reported a significantly greater decrease in knee pain at 68 weeks, as measured by the Western Ontario and McMaster University Osteoarthritis (WOMAC) index. At baseline, the mean WOMAC pain score was 70.9 points, which fell by 41.7 points among patients treated with semaglutide, compared with 27.5 points in the placebo group, a significant 14.1-point difference.
A significant benefit of semaglutide over placebo was also seen for secondary endpoints at week 68. Specifically, 87% of participants in the semaglutide group achieved at least a 5% reduction in bodyweight, compared with 29.2% of those in the placebo group. Additionally, 70.4% of semaglutide-treated participants achieved a 10% or greater reduction in bodyweight, versus 9.2% in the placebo group.
Functional improvements with semaglutide treatment were also evident, with a mean significant improvement of 41.5 points in their WOMAC physical function score, compared with 26.7 points in the placebo group. Similarly, the SF-36 physical function scale showed significant gains in semaglutide-treated participants, who had an average 12.0-point increase, compared with a 6.5-point increase for those treated with placebo.
Rates of serious adverse events were similar between the two groups, at 10.0% with semaglutide and 8.1% with placebo, and were consistent with those previously reported for GLP-1 receptor agonists, say the researchers. In total, 6.7% of patents in the semaglutide group discontinued treatment, most often due to gastrointestinal side effects (2.2%), as did 3.0% of those in the placebo group.
Bliddal and colleagues note that the participants had a high baseline BMI, with 41% classified as severely obese, and their pain scores were elevated compared with other osteoarthritis studies. They therefore recommend further research “to confirm whether these benefits extend to patients with less severe obesity or milder osteoarthritis.”
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