Influence of GLP-1 Receptor Agonists on Surgical and Nonsurgical Treatment of Ankle Osteoarthritis

Background Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used for the treatment of obesity and type 2 diabetes mellitus (T2DM), with established metabolic benefits. However, their influence on musculoskeletal outcomes, particularly in patients with ankle osteoarthritis (OA), remains unclear. Methods We conducted a retrospective cohort study using the TriNetX Analytics Network to evaluate the association between GLP-1 therapy and surgical or nonsurgical interventions for ankle OA. Adults with obesity (body mass index [BMI] ≥30 kg/m 2 ) or T2DM (ICD-10: E11) were identified between 2016 and 2020. Patients were stratified by GLP-1 use, defined as ≥2 prescriptions separated by ≥6 months for semaglutide, liraglutide, dulaglutide, exenatide, or lixisenatide. Outcomes included ankle joint injection (CPT: 20605, 20606), ankle arthroscopy/debridement (CPT: 29891, 29898, 29897, 29895), and total ankle arthroplasty (TAA) or arthrodesis (CPT: 27700, 27702, 27870, 29899). Outcomes were analyzed beginning 6 months after index date. Hazard ratios (HRs) were estimated with 95% confidence intervals (CIs). Results After matching, 3089 obese and 8117 diabetic patients were included in each comparison group. In the obese cohort, GLP-1 users had a lower risk of ankle joint injection (HR = 0.8, 95% CI = 0.6-0.9) and TAA (HR = 0.5, 95% CI = 0.3-0.9), while risk of arthroscopy was not significantly different. In the diabetic cohort, GLP-1 use was associated with increased risk of arthroscopy (HR = 1.9, 95% CI = 1.2-3.2) but not joint injection or TAA. Over 5 years, GLP-1 users achieved greater reductions in BMI compared with non-users (obese cohort: −2.7 vs −1.6 kg/m 2 ; diabetic cohort: −2.1 vs −1.7 kg/m 2 ; both P < .01). HbA1c improved significantly in both diabetic groups, with slightly greater reduction in non-users (−6.0% vs −5.5%, P < .01) Conclusion Obese GLP-1 users demonstrated lower rates of invasive ankle procedures, while diabetic GLP-1 users experienced higher arthroscopy utilization. These findings suggest that metabolic improvements may not uniformly translate to musculoskeletal benefit, warranting further investigation. Level of Evidence: III