A recent study published in the New England Journal of Medicine revealed that once-weekly injections of semaglutide significantly reduced both body weight and knee pain in individuals with obesity suffering from moderate knee osteoarthritis. The trial enrolled 407 participants with a body mass index (BMI) of 30 or higher and a confirmed diagnosis of moderate knee osteoarthritis accompanied by at least moderate pain. The participants were randomly assigned in a 2:1 ratio to receive either a weekly subcutaneous injection of semaglutide (2.4 mg) or a placebo. Both groups also received counseling on physical activity and a reduced-calorie diet.
Results demonstrated a remarkable mean weight reduction of 13.7% in the semaglutide group compared to 3.2% in the placebo group. This weight loss was accompanied by a significant decrease in knee pain, with the semaglutide group showing an average improvement of 41.7 points on the WOMAC pain scale, while the placebo group improved by only 27.5 points. Additionally, participants receiving semaglutide experienced better physical function, as indicated by a 12-point increase on the SF-36 physical-function score, compared to a 6.5-point increase in the placebo group. Despite the positive outcomes, there were some adverse events reported. Serious adverse events were similar across both groups, though 6.7% of those in the semaglutide group discontinued the treatment due to side effects, primarily gastrointestinal issues, compared to 3.0% in the placebo group.
Semaglutide enhances incretin function by activating GLP-1 receptors, leading to several beneficial effects. It increases insulin secretion in a glucose-dependent manner, inhibits glucagon release, and suppresses hepatic gluconeogenesis, thereby lowering both fasting and postprandial glucose levels. Additionally, semaglutide has demonstrated a favorable proinsulin-to-insulin ratio, indicating improved β-cell function and enhanced insulin production. Studies have also shown that semaglutide improves insulin sensitivity, likely driven by its significant impact on reducing body weight. Furthermore, its weight loss benefits are attributed to reduced energy intake and delayed gastric emptying. A study by Baser et al. found that semaglutide use was linked to a 16% reduction in the risk of OA among patients with obesity compared to those not receiving the medication. These findings suggest that semaglutide could be an effective strategy for preventing and managing OA in obese patients, potentially alleviating both the clinical and economic burden associated with the condition.
While lifestyle interventions, such as diet and exercise, are fundamental to weight management, maintaining long-term weight loss remains difficult. Clinical guidelines recommend adjunctive pharmacotherapy, especially for adults with a BMI of 30 or higher, or 27 or higher in individuals with comorbidities. However, the use of existing medications is constrained by their modest efficacy, safety concerns, and high cost.
The findings suggest that semaglutide could be a promising option for managing obesity-related knee osteoarthritis, offering significant improvements in weight loss and pain relief. These results highlight the potential of semaglutide to not only address obesity but also alleviate the debilitating symptoms of osteoarthritis, potentially transforming the management of this common condition in obese patients.
References
- Bliddal H, Bays H, Czernichow S, Uddén Hemmingsson J, Hjelmesæth J, Hoffmann Morville T, Koroleva A, Skov Neergaard J, Vélez Sánchez P, Wharton S, Wizert A, Kristensen LE; STEP 9 Study Group. Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis. N Engl J Med. 2024 Oct 31;391(17):1573-1583.
- Mahapatra MK, Karuppasamy M, Sahoo BM. Semaglutide, a glucagon like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes. Rev Endocr Metab Disord. 2022 Jun;23(3):521-539.
- Baser O, Rodchenko K, Vivier E, Baser I, Lu Y, Mohamed M. The impact of approved anti-obesity medications on osteoarthritis. Expert Opin Pharmacother. 2024 Aug;25(11):1565-1573.