Knee pain from osteoarthritis - can weight management medication help?

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Pain due to osteoarthritis can be debilitating, and my patients often tell me how this pain impairs their quality of life. Obesity-related knee osteoarthritis is caused not only by increased weight stress on the joints, but also by the chronic inflammatory state that is seen in obesity. We know that weight loss can improve pain and physical function in people with knee osteoarthritis, but osteoarthritis of the knee is a catch-22, in that pain can often limit the capacity to be physically active. Now, new data shows for the first time that a weight management medication – semaglutide 2.4mg (Wegovy) – can improve knee pain in people with obesity and knee osteoarthritis.

The STEP 9 study included 407 adults with obesity and a clinical diagnosis of moderate knee osteoarthritis, with moderate Xray changes, and a pain score of at least 40 on the WOMAC pain scale (scale of 0-100, higher scores reflecting worse pain). Participants were randomized to receive semaglutide 2.4mg (Wegovy) or placebo in a 2:1 ratio in addition to lifestyle changes (reduced calorie diet and physical activity) for 68 weeks. The primary endpoints were change in body weight and change in the WOMAC pain score.

Most people in the study were women (81.6%), average age was 56, and baseline body mass index (BMI) was 40.3. Weight loss was -13.7% with semaglutide at 68 weeks vs -3.2% with placebo. The WOMAC pain score decreased by an average of -41.7 points with semaglutide vs -27.5 points with placebo. People in the semaglutide group also had a greater increase in physical function ( as reported on SF-36 physical function score) than the placebo group (12 vs 6.5 points respectively). There was less NSAID or acetaminophen use for pain in both groups, but to a greater extent in the semaglutide group.

The reasons for improvement in pain are likely some combination of reduction in weight and reduction in inflammation (the available analyses of this study does not parse this out for us). Another GLP1 receptor agonist weight loss medication, liraglutide 3mg (Saxenda), did not show an improvement in knee osteoarthritis pain in a study done several years ago. The liraglutide group only lost -2.8kg in that study, so perhaps more weight reduction (and/or a more powerful reduction in inflammation) is needed to see benefits.

BOTTOM LINE: Semaglutide 2.4mg (Wegovy) is the first weight management medication to demonstrate an improvement in knee pain in people living with obesity and knee osteoarthritis (OA). I am excited to see the osteoarthritis field expand to definitively include weight management medication as a key aspect of treatment in people with obesity and knee OA. I’m also really excited to see this space evolve as other weight management medications are studied as treatment of knee OA as well!

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