Semaglutide and Knee
Osteoarthritis: What the Research Shows

Knee osteoarthritis (OA) can cause pain, stiffness, and difficulty with daily activities. STEP 9 is one defined study, not a reason to postpone an OA evaluation, rehabilitation, or a surgical discussion when appropriate.^{[1] [5] [6]}

What STEP 9 actually tested

STEP 9 was a 68-week, double-blind, randomized, placebo-controlled phase 3 trial. It enrolled 407 adults with body mass index (BMI) at least 30, clinical and radiologic moderate knee OA, and at least moderate pain. Participants received once-weekly subcutaneous semaglutide 2.4 mg or placebo in a 2:1 ratio, with physical-activity and reduced-calorie-diet counseling.^[1]

The enrolled group had a mean age of 56 years, mean BMI of 40.3, and mean WOMAC pain score of 70.9; 81.6% were women. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) measures patient-reported OA symptoms and lower-extremity function. Its pain score was normalized to 0–100, where higher means worse pain.^{[1] [2]}

The study is not direct evidence for every person with knee pain, every OA severity, a replaced knee, diabetes, another dose or route, or a non-study product. Its averages do not determine whether a particular person is a medication candidate.

Weight, pain, and physical function: the results in their own units

The primary endpoints were percentage change in body weight and WOMAC pain change at week 68. A key confirmatory secondary endpoint was the 36-Item Short Form Health Survey (SF-36), version 2, physical-function score. This score runs from 0 to 100, with higher scores meaning better function. A percentage weight change is not a pain-point change.^{[1] [2]}

All three comparisons favored semaglutide (P<0.001 in the published abstract). The placebo-and-counseling group also improved on pain and function. These group averages do not predict a person’s pain relief, mobility, weight change, or ability to avoid another treatment.^[1]

The absolute numbers are useful because they show the scale used for each outcome: pain fell by 41.7 points with semaglutide and 27.5 with placebo, while physical function rose by 12.0 and 6.5 points. The weight figures are percentages of baseline weight, so the 10.5-percentage-point difference is not a 10.5-pound result. Each comparison needs its own unit and trial context.

What the trial can—and cannot—show about the joint

STEP 9 shows greater average improvement with the defined regimen than placebo in this population; it does not prove why pain changed. The trial was not designed to separate a direct joint-tissue effect from effects related to greater weight reduction or the study context.

It did not establish structural repair, reversal of OA, prevention of knee replacement, or that medication can replace physical therapy or surgery. A lower pain score is not a cure and does not settle the cause of knee pain, joint damage, or the right next step for one person.^{[1] [5]}

Novo Nordisk funded the trial, which also reports industry and academic/clinical affiliations. One sponsor-funded trial should be interpreted within its population, duration, outcomes, and limitations.^[1]

Safety and clinician review still matter

In STEP 9, serious adverse events occurred at a similar rate in the two groups. Permanent discontinuation occurred in 6.7% with semaglutide and 3.0% with placebo; gastrointestinal disorders were the most common reason for stopping the trial regimen.^[1]

The current Wegovy label lists common adverse reactions including nausea, diarrhea, vomiting, constipation, abdominal pain, headache, and fatigue. Important warnings and precautions include pancreatitis, gallbladder disease, kidney injury due to volume depletion, severe gastrointestinal reactions, hypersensitivity, and procedure-related aspiration. It is contraindicated with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN 2), and with prior serious hypersensitivity to semaglutide or its excipients.^[3]

This is not a personal safety screen. A clinician and pharmacist need the exact product, health history, current medicines, pregnancy plans, and planned procedures. Do not change a prescription based on trial averages.

Knee OA is not a current FDA indication

As of September 19, 2026, the FDA Wegovy label lists weight-reduction and maintenance uses in defined populations, cardiovascular-risk reduction in a defined population, and an indication for noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis in adults for the injection. It does not list knee osteoarthritis. STEP 9 does not change label status.^[3]

STEP 9 concerns a once-weekly injectable 2.4 mg regimen. It should not be generalized automatically to other doses, oral products, other brands, or products outside the regulated supply chain.

Branded-product evidence is not compounded-product evidence

FDA says unapproved GLP-1 versions, including compounded products, do not undergo FDA review for safety, effectiveness, or quality before marketing. A compounded drug may be appropriate when a patient’s medical needs cannot be met by an FDA-approved drug, but it is not FDA approved. FDA also describes dosing, multi-dose-vial, shipping/storage, and semaglutide-salt-form concerns.^[4]

STEP 9 cannot establish a compounded preparation’s quality, bioequivalence, dose behavior, safety, or effectiveness. It is inaccurate to call a compounded preparation “the same as” the studied or FDA-approved finished product.

Knee-OA care remains multimodal

NIAMS describes OA care as a plan that may include education, exercise, weight management, prescribed braces or orthotics, symptom medicines, and sometimes surgery. The ACR/Arthritis Foundation strongly recommends exercise, weight loss for people with knee or hip OA who are overweight or have obesity, and self-management programs.^{[5] [6]}

CDC describes low-stress options such as walking, cycling, swimming, water exercise, and tai chi, and advises starting slowly and seeking care if symptoms are severe. A physical therapist can tailor activity. A trial result should not replace that assessment or a surgical evaluation when major limits need attention.^[7]

NIDDK emphasizes that weight-management medication does not replace healthy eating or physical activity. A clinician-guided plan can coordinate knee diagnosis, function, symptom relief, rehabilitation, and referrals.^[8]

Frequently asked questions