The Impact of Contemporary Glucagon-like Peptide-1 Receptor Agonists on the Onset, Severity, and Conversion to Arthroplasty in Hip and Knee Osteoarthritis

Background: The growing popularity of glucagon-like peptide-1 receptor agonists (GLP-1-RAs) for weight loss could significantly impact joint preservation and arthroplasty. While this will in part be driven by the association between obesity, osteoarthritis (OA), and total joint arthroplasty (TJA), recent evidence also indicates that GLP-1-RAs may have direct joint-protective, anti-inflammatory effects.Purpose: To evaluate the association between GLP-1-RA use and the onset and progression of hip and knee OA in an obese population.Study Design: Cohort study; Level of evidence, 3.Methods: A national health network was queried for patients with an index visit between June 1, 2021, and January 1, 2023, and a body mass index (BMI) >= 30. Patients were stratified into groups without (n = 1,092,225) and with(n = 237,043) preexisting hip and/or knee OA. One-to-one propensity score matching was used to balance GLP-1-RA use based on age, sex, race, BMI, and comorbid type 2 diabetes mellitus. Primary outcomes were incidence of hip OA, knee OA, major joint injections, total hip arthroplasty (THA), and total knee arthroplasty (TKA) within 1 year. Cox proportional hazards models were used to estimate hazard ratios (HRs) between cohorts prescribed and not prescribed GLP-1-RAs.Results: In patients with preexisting OA, GLP-1-RA use correlated with reduced odds of conversion to THA (1.1% vs 2.2%; HR, 0.6; 95% CI, 0.5 to 0.8) and TKA (1.4% vs 2.1%; HR, 0.8; 95% CI, 0.6 to 0.9) within 1 year. In patients without preexisting OA, GLP-1-RA use was associated with an increased incidence of hip OA (0.9% vs 0.7%; HR, 1.4; 95% CI, 1.2 to 1.6), knee OA (2.1% vs 1.9%; HR, 1.3; 95% CI, 1.2 to 3.1), major joint injections (2.2% vs 1.8%; HR, 1.4; 95% CI, 1.3 to 1.5), and TKA (0.09% vs 0.04%; HR, 2.6; 95% CI, 1.6 to 4.3). Comparing cohorts without prior OA, patients who were prescribed a GLP-1-RA demonstrated slightly greater decreases in BMI (-1.00; 95% CI, -1.06 to -0.96) at 1-year after the index visit compared with patients not prescribed a GLP-1-RA (-0.90; 95% CI, -0.94 to -0.84). However, in patients with a prior diagnosis of hip or knee OA, there was no difference noted in BMI change.Conclusion: GLP-1-RAs may provide direct disease-modifying behaviors in patients with preexisting OA diagnosis, per a reduced risk of conversion to TJA not attributable to weight loss. Further investigation is also needed to elucidate the association between GLP-1-RA use and the increased incidence of OA diagnosis and conversion to TKA in patients with no preexisting OA diagnosis.