Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis

Bliddal H, Bays H, Czernichow S, Uddén Hemmingsson J, Hjelmesæth J, Hoffmann Morville T, Koroleva A, Skov Neergaard J, Vélez Sánchez P, Wharton S, Wizert A, Kristensen LE · The New England Journal of Medicine

The largest and longest test yet of the proposition this entry rests on — that taking weight off a knee makes it hurt less. Body weight fell 13.7% on semaglutide and 3.2% on placebo (p < 0.001). WOMAC pain fell 41.7 points on semaglutide and 27.5 on placebo (p < 0.001) on a 0-100 scale, and SF-36 physical function rose 12.0 versus 6.5 points (p < 0.001). Serious adverse events were similar; discontinuation for adverse events was 6.7% versus 3.0%, mostly gastrointestinal.

Population

407 adults with BMI ≥ 30 and clinically and radiologically diagnosed moderate knee osteoarthritis with at least moderate pain; mean age 56, mean BMI 40.3, mean WOMAC pain 70.9, 81.6% women, 61 sites in 11 countries

Intervention

Once-weekly subcutaneous semaglutide 2.4 mg for 68 weeks, plus counselling on activity and a reduced-calorie diet

Comparator

Placebo plus the same counselling, 2:1 allocation

Limitations

Funded by Novo Nordisk, with four authors employed by the company. Both arms received activity and diet counselling and both improved substantially — the placebo arm's 27.5-point fall is most of the semaglutide arm's — so the trial measures the increment a drug adds to lifestyle advice. Symptom and function endpoints only; no imaging, so nothing here speaks to cartilage. 68 weeks. Registered NCT05064735.