Journal Article

Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis

Hjelmesæth, Jøran, Koroleva, Anna, Wharton, Sean, Bays, Harold, Uddén Hemmingsson, Joanna, Kristensen, Lars E., Bliddal, Henning, Skov Neergaard, Jesper, Vélez Sánchez, Patricia, Czernichow, Sébastien, Hoffmann Morville, Thomas, Wizert, Alicja

2024

Overview

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. 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). 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. 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.).

• Publisher: Massachusetts Medical Society
• Subject: Adverse events / Aged / Aging / Aging General / Antidiabetics / Arthralgia - diagnosis / Arthralgia - etiology / Arthralgia - therapy / Body Mass Index / Body weight / Caloric Restriction / Clinical Medicine / Clinical Medicine General / Clinical trials / Combined Modality Therapy / Counseling / Double-Blind Method / Drug Administration Schedule / Drug dosages / Drug overdose / Endocrinology / Endocrinology General / Exercise / Female / Gastroenterology / Gastroenterology General / Gastrointestinal diseases / Gastrointestinal surgery / Geriatrics / GLP-1 receptor agonists / Glucagon / Glucagon-like peptide 1 / Glucagon-Like Peptide-1 Receptor Agonists - administration & dosage / Glucagon-Like Peptide-1 Receptor Agonists - adverse effects / Humans / Injections, Subcutaneous / Knee / Life Sciences / Male / Middle Aged / Obesity / Obesity - complications / Obesity - therapy / Orthopedics / Orthopedics General / Osteoarthritis / Osteoarthritis, Knee - complications / Osteoarthritis, Knee - therapy / Outpatient-Based Clinical Medicine / Pain / Pain Measurement / Physical activity / Placebos / Rehabilitation / Rheumatology / Rheumatology General / Statistical analysis / Weight control / Weight Loss - drug effects / Well being