Semaglutide Eased Knee Osteoarthritis Pain More Than Placebo

CATEGORY: MOBILITY, BONES & JOINTS

In a 68-week randomized trial of 407 adults with obesity and moderate knee osteoarthritis, weekly injections of the weight-loss drug semaglutide were followed by an average 41.7-point drop in knee pain on a 100-point scale—compared with a 27.5-point drop among those given a placebo.¹ Osteoarthritis is the common, wear-related form of arthritis in which the cartilage that cushions a joint gradually breaks down, and the knee is one of its most frequent targets.

61 Sites, 11 Countries, WOMAC Pain Scores

Researchers at 61 sites in 11 countries enrolled adults with a body-mass index of 30 or higher—the standard threshold for obesity—and a confirmed diagnosis of moderate knee osteoarthritis with at least moderate pain. Participants were randomly assigned, two to one, to a weekly semaglutide injection or an identical-looking placebo, and neither they nor the researchers knew who received which. Body weight change and knee pain score were the trial’s prespecified primary endpoints, and semaglutide outperformed placebo on both.¹ Everyone also got the same counseling on physical activity and eating habits. Pain was scored at the start and again at week 68 on the WOMAC scale, a standard 100-point arthritis questionnaire in which higher numbers mean worse pain. The typical participant was a 56-year-old woman starting at a pain score of about 71.

Weight Fell 13.7% Versus 3.2% With Placebo

By week 68, pain scores had fallen by 41.7 points in the semaglutide group versus 27.5 points with placebo—a difference of roughly 14 points on the 100-point scale. Body weight fell 13.7% with semaglutide versus 3.2% with placebo, and a standard measure of physical function improved nearly twice as much. Serious side effects were similar in the two groups, though stomach and digestive complaints led 6.7% of semaglutide users to stop treatment, compared with 3.0% on placebo.

Knees Carry a Multiple of Your Body Weight

Your knees carry a multiple of your body weight with every step, so shedding weight takes a magnified load off damaged cartilage. Fat tissue also releases inflammatory signals that may sensitize joints, meaning weight loss may quiet pain chemically as well as mechanically. The placebo group’s own 27.5-point improvement is a reminder of how strong the response to counseling, attention and expectation can be in pain studies—the drug’s added benefit sits on top of that.

Funded by Novo Nordisk and Ended at 68 Weeks

All participants had obesity and at least moderate pain, so the results say nothing about people with lower body weight or milder arthritis. The trial ended at 68 weeks, so it cannot say how long relief lasts or whether it persists if the drug is stopped. It was funded by Novo Nordisk, the company that makes semaglutide—a routine arrangement in drug trials, but worth knowing when weighing the evidence.

28% Lower Knee Replacement Rate Over Eight Years

Other research on GLP-1 drugs—the class semaglutide belongs to—points the same way. In a Shanghai cohort of people with knee osteoarthritis and type 2 diabetes, those taking these drugs had modestly lower pain scores than those who did not, though tracking studies like this show association, not cause.² In a large database analysis, three years of semaglutide or tirzepatide was linked to a 28% lower rate of knee replacement over eight years.³

Key Takeaways

• In adults with obesity and moderate knee osteoarthritis, weekly semaglutide was associated with a 41.7-point drop in knee pain on a 100-point scale over 68 weeks, versus 27.5 points with placebo.
• Because participants were randomly assigned and blinded, this is stronger evidence than an observational study; both groups also received activity and eating counseling.
• Weight fell 13.7% with semaglutide versus 3.2% with placebo; digestive complaints were the most common reason for stopping the drug.
• The trial covered people with obesity and moderate-to-severe knee pain, so the findings do not extend to milder arthritis or lower body weights.

References

1. Bliddal H, Bays H, Czernichow S, et al. Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis. New England Journal of Medicine. 2024;391(17):1573–1583. link
2. Zhu H, Zhou L, Wang Q, et al. Glucagon-like peptide-1 receptor agonists as a disease-modifying therapy for knee osteoarthritis mediated by weight loss: findings from the Shanghai Osteoarthritis Cohort. Annals of the Rheumatic Diseases. 2023;82(9):1218–1226. link.
3. Carter V, Desverreaux E, Amin I, et al. Glucagon-like peptide 1 receptor agonist use and risk of arthroplasty for knee osteoarthritis: retrospective database analysis. Regional Anesthesia and Pain Medicine. 2026;rapm-2026-107658. link.