Literature
Clinical Pearls & Morning Reports
Published October 30, 2024
Bliddal et al. conducted a randomized, placebo-controlled trial that assessed semaglutide (a glucagon-like peptide-1 receptor agonist) as an adjunct to lifestyle modifications in reducing body weight and pain related to knee osteoarthritis in participants with obesity, clinical and radiologic diagnosis of moderate knee osteoarthritis, and knee pain that was at least moderately severe. Read the NEJM Original Article here.
Clinical Pearls
Q: Is obesity-related knee osteoarthritis solely a result of increased mechanical stress on the joint?
A: Osteoarthritis of the knee represents the most prevalent form of osteoarthritis and leads to chronic pain, reduced mobility, disability, and impaired quality of life. Obesity is a major risk factor for the development and progression of osteoarthritis of the knee. Obesity-related knee osteoarthritis arises from a combination of increased mechanical stress on weight-bearing joints, metabolic dysfunction, and obesity-induced inflammation.
Q: What do treatment guidelines recommend as first-line management of obesity-related knee osteoarthritis?
A: Treatment guidelines recommend weight reduction and physical activity as first-line management for obesity-related knee osteoarthritis. Clinically important weight reduction requires a combination of a reduced-calorie diet and patient-centered physical-activity interventions, which may be challenging to adhere to but have been shown to improve patient-reported outcomes related to pain. There remains an unmet need for weight-management medications that can facilitate nonsurgical, sustained weight reduction and reduce pain in persons with obesity-related knee osteoarthritis.
A: The primary end points of this trial were the percentage change in body weight and the change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score (on a scale of 0 to 100, with higher scores reflecting worse outcomes) from baseline to week 68. A total of 407 participants were enrolled. The mean age was 56 years, the mean body-mass index was 40.3, and the mean WOMAC pain score 70.9. A total of 81.6% of the participants were women. The mean change in body weight from baseline to week 68 was -13.7% with semaglutide and -3.2% with placebo (P<0.001). The mean change in the WOMAC pain score at week 68 was -41.7 points with semaglutide and -27.5 points with placebo (P<0.001). Participants in the semaglutide group had a greater improvement in the physical-function score on the 36-Item Short Form Health Survey than those in the placebo group (mean change, 12.0 points vs. 6.5 points; P<0.001).
A: The trial was not designed to investigate the mechanism of action of semaglutide on knee osteoarthritis, so mechanistic conclusions cannot be drawn. Weight reduction is most likely a major contributor, as a result of reduced mechanical stress on the knee joints; previous studies have shown that weight reduction through various strategies can lead to considerable alleviation of knee pain and joint stiffness. Preclinical studies have shown that glucagon-like peptide-1 receptor agonists have antiinflammatory and antidegradative effects.