Glucagon-like peptide-1 receptor agonists as a disease-modifying therapy for knee osteoarthritis mediated by weight loss: findings from the Shanghai Osteoarthritis Cohort

May 31, 2023Annals of the rheumatic diseases

Glucagon-like peptide-1 receptor agonists as treatments that may change knee osteoarthritis by causing weight loss: results from the Shanghai Osteoarthritis Cohort

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Abstract

GLP-1 receptor agonists (GLP-1RAs) are associated with a 7.29 kg weight loss and a lower incidence of knee surgery in knee osteoarthritis patients with type 2 diabetes.

GLP-1RA therapy resulted in a lower incidence of knee surgery (1.7% for GLP-1RA vs 5.9% for non-GLP-1RA, adjusted p=0.014).
Participants using GLP-1RAs showed significant improvements in knee pain and function, with a reduction in WOMAC total score by 1.46 and pain subscore by 3.37.
The velocity of cartilage loss in the medial femorotibial joint was significantly reduced in the GLP-1RA group, with an adjusted mean difference of -0.02 mm (p=0.004).
Within the GLP-1RA group, there was a significant decrease in symptom-relieving medication consumption after treatment compared to before treatment.
Weight reduction may mediate the relationship between GLP-1RA exposure and decreased incidence of knee surgery, accounting for 32.1% of the observed effect.

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OBJECTIVE: Obesity is a risk factor for knee osteoarthritis (KOA) development and progression. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are indicated for type 2 diabetes mellitus (T2DM) and obesity. However, whether KOA patients can benefit from GLP-1RA therapies has not been sufficiently investigated, especially in the long term.

METHODS: The Shanghai Osteoarthritis Cohort study is a prospective, observational, multicentre study of >40 000 adults with clinically diagnosed osteoarthritis aged >45 years in Shanghai. We identified all KOA participants with comorbid T2DM enrolled from 1 January 2011 to 1 January 2017. Primary outcome was incidence of knee surgery after enrolment. Secondary outcomes included pain-relieving medication use, number of intra-articular therapies, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and medial femorotibial joint cartilage thickness. To evaluate the effects of GLP-1RA, we performed before-and-after comparison and comparison with participants who had no GLP-1RA exposure.

RESULTS: For an intergroup comparison (non-GLP-1RA vs GLP-1RA), more weight loss (adjusted mean difference in weight change from baseline -7.29 kg (95% CI -8.07 to -6.50 kg), p<0.001) and lower incidence of knee surgery (93/1574 (5.9%) vs 4/233 (1.7%), adjusted p=0.014) were observed in the GLP-1RA group. Statistically significant differences in mean change from baseline for the WOMAC total and pain subscale scores were observed (adjusted mean difference in WOMAC total score -1.46 (95% CI -2.84 to -0.08), p=0.038; adjusted mean difference in WOMAC pain subscore -3.37 (95% CI -5.79 to -0.94), p=0.007). Cartilage-loss velocity of the medial femorotibial joint was significantly lower in the GLP-1RA group postadjustment for baseline characteristics (adjusted mean difference -0.02 mm (95% CI -0.03 to -0.002 mm), p=0.004). For the before-and-after comparison within the GLP-1RA group, we observed a significant decrease of symptom-relieving medication consumption and cartilage loss velocity of medial femorotibial joint (after-treatment vs before-treatment: -0.03±0.05 vs -0.05±0.07 mm/year, p<0.001). The association between GLP-1RA exposure and decreased incidence of knee surgery was mediated by weight reduction (mediation proportion: 32.1%), instead of glycaemic control (too small to calculate).

CONCLUSION: With sufficient treatment duration, GLP-1RA therapies might be disease-modifying for KOA patients with comorbid T2DM, possibly mediated by weight loss. Further investigation is needed to elucidate effects of GLP-1RA on disease process, joint structure and patient-reported outcomes of osteoarthritis.

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Glucagon-like peptide-1 receptor agonists as a disease-modifying therapy for knee osteoarthritis mediated by weight loss: findings from the Shanghai Osteoarthritis Cohort

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