Glucagon-like peptide-1 receptor agonists for osteoarthritis: a systematic review

Background Obesity is a major risk factor for osteoarthritis and contributes through mechanical loading, inflammation and metabolic dysfunction. GLP-1 agonists are highly effective anti-obesity medications with potential relevance to obesity-related osteoarthritis. This review evaluated their therapeutic effects against the OMERACT-OARSI Core Outcomes. Methods A comprehensive search of MEDLINE, EMBASE, Scopus, CINAHL, Cochrane CENTRAL and ClinicalTrials.gov was performed with research librarian guidance. Articles were screened by two blinded authors. Studies were assessed for risk of bias using Cochrane ROB2 and ROBINS-I. Study methods were guided by the Cochrane Handbook and reporting is per PRISMA. Results 910 unique abstracts were screened. Two randomised controlled trials and five observational studies on a total of 160,089 patients were included. Heterogeneity precluded meta-analysis, so data were narratively synthesised. The strongest evidence came from RCTs: semaglutide produced a 14.1-point greater improvement in WOMAC pain (0–100 scale) than placebo, with improvement in physical function also reported. Observational studies suggested lower conversion to hip arthroplasty (HR 0.60) and knee arthroplasty (HR 0.75), and slower knee cartilage loss (adjusted mean difference 0.02 mm/year), but these findings were of lower certainty. Conclusions Preliminary evidence suggests that GLP-1 RAs may improve pain and physical function in people with obesity and knee osteoarthritis. Evidence that they alter structural progression or reduce conversion to arthroplasty is low-certainty and observational. High-quality osteoarthritis-specific RCTs with longer follow-up and integrated economic analyses are required before disease-modifying or arthroplasty-sparing effects can be established.