GLP-1RA Therapy Effective in Combating Knee Osteoarthritis in T2D Patients

Obesity has long been known as a risk factor for the development and progression of knee osteoarthritis (KOA). However, a recent research from the Shanghai Osteoarthritis Cohort study suggests that Glucagon-like peptide-1 receptor agonists (GLP-1RAs), commonly used to treat type 2 diabetes mellitus (T2DM) and obesity, may offer significant benefits to KOA patients, especially when it comes to long-term treatment. The findings were published in the 

In a prospective, observational, multicenter study involving over 40,000 adults with clinically diagnosed osteoarthritis aged over 45 years in Shanghai, researchers focused on identifying KOA patients with comorbid T2DM enrolled between January 2011 and January 2017. The primary outcome of the study was the incidence of knee surgery after enrollment, while secondary outcomes included pain-relieving medication use, intra-articular therapies, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and medial femorotibial joint cartilage thickness.

The findings revealed that KOA patients treated with GLP-1RAs experienced significant improvements compared to those without exposure to this therapy. One notable benefit was substantial weight loss, with an adjusted mean difference in weight change from baseline of -7.29 kg (95% CI -8.07 to -6.50 kg, p<0.001). The GLP-1RA group also exhibited a lower incidence of knee surgery, with only 1.7% requiring surgery compared to 5.9% in the non-GLP-1RA group (adjusted p=0.014).

Moreover, the WOMAC total and pain subscale scores showed significant improvements in the GLP-1RA-treated group, indicating better overall joint function and reduced pain. The cartilage-loss velocity of the medial femorotibial joint was also significantly lower in the GLP-1RA group, suggesting a potential disease-modifying effect of the therapy.

In an additional before-and-after comparison within the GLP-1RA group, researchers observed a significant decrease in symptom-relieving medication consumption and cartilage loss velocity of the medial femorotibial joint. This indicates that GLP-1RA therapies may not only mitigate KOA symptoms but potentially modify the disease process itself.

Interestingly, the study also found that the decreased incidence of knee surgery in GLP-1RA-treated patients was predominantly mediated by weight reduction (mediation proportion: 32.1%), rather than improved glycaemic control.

Source:

Zhu, H., Zhou, L., Wang, Q., Cai, Q., Yang, F., Jin, H., Chen, Y., Song, Y., & Zhang, C. (2023). Glucagon-like peptide-1 receptor agonists as a disease-modifying therapy for knee osteoarthritis mediated by weight loss: findings from the Shanghai Osteoarthritis Cohort. Annals of the Rheumatic Diseases. https://doi.org/10.1136/ard-2023-223845