Abstract
ObjectiveObesity 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.MethodsThe 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.ResultsFor 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).ConclusionWith 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.
Funder
National Natural Science Foundation of China
Shanghai Shen Kang Hospital Development Center, Clinical Research Plan of SHDC
Subject
General Biochemistry, Genetics and Molecular Biology,Immunology,Immunology and Allergy,Rheumatology
Cited by
5 articles.
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