• Henning Bliddal, Harold Bays, Sébastien Czernichow, Uddén HemmingssonJoannaJFrom the Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen (H. Bliddal, L.E.K.), and Novo Nordisk, Søborg (T.H.M., A.K., J.S.N., A.W.) - both in Denmark; Louisville Metabolic and Atheroscl, Jøran Hjelmesæth, Thomas Hoffmann Morville, Anna Koroleva, Skov NeergaardJesperJFrom the Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen (H. Bliddal, L.E.K.), and Novo Nordisk, Søborg (T.H.M., A.K., J.S.N., A.W.) - both in Denmark; Louisville Metabolic and Atherosclero, Patricia Vélez Sánchez, Sean Wharton, Alicja Wizert, Lars E Kristensen, and STEP 9 Study Group.
• From the Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen (H. Bliddal, L.E.K.), and Novo Nordisk, Søborg (T.H.M., A.K., J.S.N., A.W.) - both in Denmark; Louisville Metabolic and Atherosclerosis Research Center, University of Louisville School of Medicine, Louisville, KY (H. Bays); the Department of Nutrition, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris (S.C.); the Obesity Department, Capio St. Göran's Hospital, and Medical Department at the Karolinska Institute, Stockholm (J.U.H.); the Department of Endocrinology, Obesity, and Nutrition, Vestfold Hospital Trust, Tønsberg, and the Department of Endocrinology, Morbid Obesity, and Preventive Medicine, Institute of Clinical Medicine, University of Oslo, Oslo - both in Norway (J.H.); Centro de Investigación en Reumatología y Especialidades Médicas, Bogota, Colombia (P.V.S.); and the University of Toronto and York University, Toronto, McMaster University, Hamilton, ON, and Wharton Medical Clinic Weight and Diabetes Management, Burlington, ON - all in Canada (S.W.).
• N. Engl. J. Med. 2024 Oct 31; 391 (17): 157315831573-1583.

BackgroundWeight reduction has been shown to alleviate symptoms of osteoarthritis of the knee, including pain. The effect of glucagon-like peptide-1 receptor agonists on outcomes in knee osteoarthritis among persons with obesity has not been well studied.MethodsWe conducted a 68-week, double-blind, randomized, placebo-controlled trial at 61 sites in 11 countries. Participants with obesity (a body-mass index [BMI; the weight in kilograms divided by the square of the height in meters] of ≥30) and a clinical and radiologic diagnosis of moderate knee osteoarthritis with at least moderate pain were randomly assigned, in a 2:1 ratio, to receive once-weekly subcutaneous semaglutide (2.4 mg) or placebo, in addition to counseling on physical activity and a reduced-calorie diet. The primary end points were the percentage change in body weight and the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score (on a scale of 0 to 100, with higher scores reflecting worse outcomes) from baseline to week 68. A key confirmatory secondary end point was the physical-function score on the 36-Item Short Form Health Survey (SF-36), version 2 (on a scale of 0 to 100, with higher scores indicating greater well-being).ResultsA total of 407 participants were enrolled. The mean age was 56 years, the mean BMI 40.3, and the mean WOMAC pain score 70.9. A total of 81.6% of the participants were women. The mean change in body weight from baseline to week 68 was -13.7% with semaglutide and -3.2% with placebo (P<0.001). The mean change in the WOMAC pain score at week 68 was -41.7 points with semaglutide and -27.5 points with placebo (P<0.001). Participants in the semaglutide group had a greater improvement in SF-36 physical-function score than those in the placebo group (mean change, 12.0 points vs. 6.5 points; P<0.001). The incidence of serious adverse events was similar in the two groups. Adverse events that led to permanent discontinuation of the trial regimen occurred in 6.7% of the participants in the semaglutide group and in 3.0% in the placebo group, with gastrointestinal disorders being the most common reason for discontinuation.ConclusionsAmong participants with obesity and knee osteoarthritis with moderate-to-severe pain, treatment with once-weekly injectable semaglutide resulted in significantly greater reductions in body weight and pain related to knee osteoarthritis than placebo. (Funded by Novo Nordisk; STEP 9 ClinicalTrials.gov number, NCT05064735.).Copyright © 2024 Massachusetts Medical Society.

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