Novo Nordisk's STEP 9 trial finds semaglutide eases knee osteoarthritis pain in adults with obesity

The New England Journal of Medicine published results Oct. 30, 2024 from STEP 9, a 68-week trial in which weekly semaglutide 2.4 mg (the drug in Ozempic, Wegovy and Rybelsus) helped adults with obesity and moderate knee osteoarthritis lose more weight and report less knee pain than placebo ^[1][2]. Semaglutide is not approved in the U.S. to treat knee osteoarthritis ^[2].

The trial enrolled 407 adults at 61 sites in 11 countries. Participants were randomly assigned in a 2-to-1 ratio to semaglutide 2.4 mg or placebo, given as a once-weekly injection, and everyone also received counseling on a reduced-calorie diet and physical activity ^[1][2]. The average age was 56, average body mass index was 40.3, 81.6% of participants were women, and the average starting WOMAC pain score was 70.9 on a 0-to-100 scale where higher numbers mean worse pain ^[1].

On weight, the average change from baseline to week 68 was –13.7% with semaglutide and –3.2% with placebo (P<0.001) ^[1]. Novo Nordisk said participants' mean starting body weight was 239.5 pounds ^[2]. A summary of the trial by RxFiles, a Canadian drug information service, describes the treatment difference as roughly 10.5% more body weight lost over 68 weeks ^[3].

On pain, the average WOMAC pain score fell 41.7 points with semaglutide and 27.5 points with placebo (P<0.001) ^[1][2]. Physical function, measured by the 36-Item Short Form Survey, improved by 12.0 points with semaglutide versus 6.5 points with placebo (P<0.001) ^[1][2].

Serious adverse events were reported in 10.0% of the semaglutide group and 8.1% of the placebo group ^[2]. Side effects that led to permanent discontinuation occurred in 6.7% of semaglutide participants and 3.0% of placebo participants, with gastrointestinal disorders the most common reason (2.2% versus 0%) ^[1][2]. The trial collected a deliberately limited set of safety data, recording only serious events, events leading to discontinuation, events requiring invasive knee procedures, medication errors, acute pancreatitis, COVID-19 and pregnancy-related events ^[2].

RxFiles lists several limitations. Because weight loss was visible, participants and investigators could likely tell who was receiving the drug, which may have influenced subjective pain reporting. The inclusion and exclusion criteria were strict, which makes the findings harder to apply to a broader patient group. The trial was not designed to show whether semaglutide relieves pain through some mechanism beyond weight loss, and it is unknown whether pain and function benefits persist long term—especially since weight often returns after the drug is stopped ^[3]. Novo Nordisk funded the trial, registered as NCT05064735 ^[1].

Why it matters for patients

Obesity is a major risk factor for knee osteoarthritis, and obesity-related knee osteoarthritis affects walking and moving around ^[2]. Weight loss and physical activity are recommended first-line approaches; RxFiles notes that about 5% total body weight loss can produce clinically meaningful improvement in pain and function ^[3].

The population studied was specific: adults with a BMI of at least 30, moderate X-ray changes in the target knee, and at least moderately severe pain, and many common conditions excluded people from joining ^[1][2][3]. Results in that group may not carry over to other patients with knee arthritis.

Both groups improved substantially, including on placebo, and both received diet and activity counseling ^[1]. Anyone currently taking semaglutide for weight or diabetes should know this trial did not test the drug as an arthritis treatment, and coverage for that use by insurers has not been reported.

What happens next

Novo Nordisk said it looks forward to working with regulatory authorities on next steps based on these findings, and stated there is no guarantee semaglutide will become commercially available for knee osteoarthritis ^[2]. No regulatory filing or decision date has been disclosed.

Participants had a seven-week follow-up period after treatment stopped ^[2][3]. Whether pain and function gains hold up after the drug is discontinued has not been established ^[3].