Five-Year Incidence of Progression to Ankle Osteoarthritis in Patients with and without Glucagon-like Peptide-1 Receptor Agonist Therapy.

Abstract

BackgroundGlucagon-like peptide-1 receptor agonists (GLP) are widely prescribed for type 2 diabetes mellitus (T2DM) and obesity, with established metabolic and anti-inflammatory benefits. Their musculoskeletal impact, particularly on joint-specific outcomes such as ankle osteoarthritis (OA), remains poorly defined.MethodsUsing the TriNetX database, we conducted a retrospective cohort study of adults treated from 2016 to 2020 with a minimum 5-year follow-up. Two main cohorts were analyzed: obese (body mass index [BMI] ≥30 kg/m²) and T2DM patients. The primary outcome was the development of ankle OA, while secondary outcomes included interventions such as joint injection, total ankle arthroplasty (TAA), and ankle arthrodesis. Propensity score matching balanced age, sex, race, BMI, HbA_1c, comorbidities, and socioeconomic variables. Subgroup analyses stratified the obese cohort by BMI groups (30-34.9, 35-39.9, 40-44.9, ≥45 kg/m²).ResultsAfter matching, 2363 obese and 37 737 diabetic patients were included. In obese patients, GLP use was not associated with a significant increase in the risk of ankle OA (odds ratio [OR] = 1.2, 95% confidence interval [CI] = 0.9-1.5). In diabetic patients, GLP use was associated with a higher risk of ankle OA (OR = 1.3, 95% CI = 1.2-1.4) and joint injection (hazard ratio [HR] = 1.3, 95% CI = 1.1-1.4). No differences were observed in the risk of surgical outcomes, including TAA or arthrodesis. Subgroup analysis revealed no consistent stepwise increase in OA risk across BMI strata in GLP users, whereas non-users demonstrated higher OA risk with increasing BMI.ConclusionThe GLP use was associated with an elevated risk of ankle OA in diabetic but not obese patients, without increased risk of surgical intervention. These findings highlight the importance of considering mechanical and biologic mechanisms unique to the ankle when assessing OA progression.Level of EvidenceLevel III: Retrospective cohort study.