Semaglutide Eased Knee Osteoarthritis Pain More Than Placebo

CATEGORY: MOBILITY, BONES & JOINTS

Weekly injections of the weight-loss drug semaglutide took an average of 41.7 points off knee pain on a 100-point scale over 68 weeks. Placebo managed 27.5 points.¹ The trial randomized 407 adults who had obesity and moderate knee osteoarthritis, the common wear-related form of arthritis in which the cartilage cushioning a joint gradually breaks down. The knee is one of its most frequent targets.

61 Sites, and a Pain Score Out of 100

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. Two of every three were allocated to a weekly semaglutide injection and one to an identical-looking placebo, the split settled by randomization rather than by choice. Nobody involved could tell one syringe from the other. Both groups received identical 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 on which higher numbers mean worse pain. The typical participant was a 56-year-old woman starting at about 71. Body weight change and knee pain score were the two prespecified primary endpoints, and semaglutide outperformed placebo on both.¹

Weight Fell 13.7% Against 3.2%

By week 68, pain scores had dropped 41.7 points with semaglutide and 27.5 points with placebo, a difference of roughly 14 points on the 100-point scale. Body weight fell 13.7% with the drug and 3.2% with placebo. A standard measure of physical function improved nearly twice as much. Serious side effects ran at similar rates in both groups, though stomach and digestive complaints led 6.7% of semaglutide users to stop treatment, against 3.0% on placebo.

A Knee Carries a Multiple of Body Weight With Every Step

Every step loads a knee with a multiple of body weight, so lost pounds take a magnified burden off damaged cartilage. Fat tissue also releases inflammatory signals that may sensitize joints, which means weight loss could quiet pain chemically as well as mechanically. The placebo group improved 27.5 points on its own. Counseling, attention and expectation move pain scores a long way in studies of this kind, and the drug’s benefit sits on top of that.

Novo Nordisk Paid for It, and It Stopped at 68 Weeks

Everyone enrolled had obesity and at least moderate pain, so the results say nothing about people at lower body weights or with milder arthritis. The trial ended at 68 weeks. How long relief lasts, and whether it survives stopping the drug, went unmeasured. The study was paid for by Novo Nordisk, which makes semaglutide, a common arrangement that still belongs in any weighing of the evidence.

Other work on GLP-1 drugs, the class semaglutide belongs to, has found something similar. 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 of that sort show association rather than cause.² A large database analysis linked three years of semaglutide or tirzepatide to a 28% lower rate of knee replacement over eight years.³

Key Takeaways

• Weekly semaglutide was followed by a 41.7-point drop in knee pain on a 100-point scale over 68 weeks, against 27.5 points with placebo, in adults with obesity and moderate knee osteoarthritis.
• Body weight fell 13.7% with semaglutide and 3.2% with placebo; digestive complaints were the most common reason for quitting the drug.
• Random allocation plus blinding puts this above a tracking study for strength of evidence, and activity and eating counseling went to both groups.
• Everyone enrolled had obesity and moderate-to-severe knee pain, so the findings do not stretch 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.