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

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.

Anti-depressant medication use is a risk factor for incident knee surgery and opioid use in patients with knee osteoarthritis

“…Glucagon-like peptide-1 receptor agonists (GLP-1RAs), including semaglutide, liraglutide, and dulaglutide, are a newly emergent class of weight-reducing drugs ( 44 ). A multicenter prospective study revealed that GLP-1RAs acted as disease-modifying drugs for KOA patients mediated by weight loss ( 2 ). Future research may need to pay more attention to this class of game-changing drugs.…”

“…Knee osteoarthritis (KOA) is a prevalent and disabling disease characterized by the structural degradation of cartilage, persistent pain, joint stiffness, and functional limitations, affecting more than 10% of the overall population as estimated (1)(2)(3). According to the Global Burden of Disease Study 2019 (4), because of the increase in the aging population, the disease burden of KOA has been rapidly growing worldwide over the past decades (5).…”

Annals of the Rheumatic Diseases collection on osteoarthritis (2018–2023): hopes and disappointments

“…They compared the level of pain, the velocity of cartilage degradation as measured by MRI and the number of knee surgeries among patients with diabetes with knee OA treated or not with GLP1RAs. They observed a significant association between GLP1RA use and all endpoints 19. Interestingly, because of the other property of these molecules to facilitate weight loss, they looked at this causal role in mediating this association and found that only 31% of this association was mediated by weight loss suggesting an additional direct effect on joints.…”

Knee Osteoarthritis in Patients With High BMI: The Role of an Orthopaedic Surgeon

“…A new class of medications (GLP-1 antagonists) have emerged with good efficacy and low side effects profile for losing weight, which could be considered. The Shanghai Osteoarthritis Cohort study prospectively followed >40 000 adults above 45 years with clinically diagnosed OA and concluded that GLP-1RA in sufficient treatment duration could be knee OA disease-modifying in patients with diabetes, possibly through weight loss [47]. However, they found a need for more investigations to clarify the effects on joint structure, disease process, and patient-reported outcomes.…”