GLP-1 Drugs and Knee Osteoarthritis: What the STEP 9 Trial Showed

Most GLP-1 benefit data comes from cardiometabolic trials. Knee osteoarthritis is different: it was studied directly, in a trial designed around the joint, in people who had both obesity and knee osteoarthritis.

This article awaits medical-reviewer signoff.

STEP 9 — semaglutide in obesity and knee osteoarthritis

Published: NEJM, 2024 Population: 407 adults with obesity and a clinical diagnosis of knee osteoarthritis with moderate radiographic changes Drug: Semaglutide 2.4 mg weekly, as an adjunct to lifestyle modification Duration: 68 weeks

Co-primary endpoints: change in body weight and change in WOMAC pain score (a standard osteoarthritis pain questionnaire).

Results:

• Pain: WOMAC pain score improved by 41.7 points on semaglutide versus 27.5 on placebo — a treatment difference of about 14 points (larger negative change = more pain relief).
• Weight: 13.7% body-weight reduction on semaglutide versus 3.2% on placebo.
• Function: physical-function scores (SF-36) improved more on semaglutide (about +12 points vs +6.5).
• Safety: gastrointestinal side effects were the most common reason for discontinuation, consistent with the rest of the semaglutide programme.

This made STEP 9 the first large randomised trial to show that a GLP-1 drug meaningfully reduces osteoarthritis pain.

Why it works

Mechanical unloading. Every kilogram of body weight multiplies the load passing through the knee during walking. Losing roughly 14% of body weight removes a substantial, repeated mechanical stress from an already damaged joint.

Lower systemic inflammation. Adipose (fat) tissue secretes inflammatory mediators that contribute to joint pain. Reducing fat mass lowers this inflammatory tone, which may add to the pain benefit beyond mechanics alone.

STEP 9 was not designed to fully separate these contributions, but both point in the same direction.

What it is not

• Not cartilage repair. STEP 9 measured pain and function, not cartilage regrowth. Semaglutide should not be described as reversing or curing osteoarthritis.
• Not an FDA-approved osteoarthritis treatment. This is a trial finding in a specific population, not an approved indication.
• Not a replacement for the basics. Exercise therapy, physiotherapy, and — where indicated — joint surgery remain central to osteoarthritis care. The trial added semaglutide on top of lifestyle modification.

Clinical implications

For people who have both obesity and symptomatic knee osteoarthritis, STEP 9 suggests a GLP-1 may reduce pain and improve function while also driving weight loss — potentially lowering reliance on NSAIDs and other painkillers for some patients. Whether a GLP-1 is appropriate is an individual decision involving your prescriber and, for the joint itself, an orthopaedic or rheumatology specialist.

Part of: GLP-1 Benefits Beyond Weight Loss. Related reading: GLP-1 drugs and bone health and exercise on GLP-1 drugs.

Editorial note: This article awaits medical-reviewer signoff. Osteoarthritis and its treatment are clinical matters; decisions about pain medication or surgery should involve the specialists managing your joint.