Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis.

Autor:	Bliddal H; 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.)., Bays H; 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.)., Czernichow S; 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.)., Uddén Hemmingsson J; 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.)., Hjelmesæth J; 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.)., Hoffmann Morville T; 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.)., Koroleva A; 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.)., Skov Neergaard J; 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.)., Vélez Sánchez P; 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.)., Wharton S; 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.)., Wizert A; 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.)., Kristensen LE; 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.).
Jazyk:	angličtina
Zdroj:	The New England journal of medicine [N Engl J Med] 2024 Oct 31; Vol. 391 (17), pp. 1573-1583.
DOI:	10.1056/NEJMoa2403664
Abstrakt:	Background: Weight 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. Methods: We 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). Results: A 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. Conclusions: Among 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.)
Databáze:	MEDLINE
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