Glucagon-like peptide-1 receptor agonists and risk of osteoarthritis among individuals with type 2 diabetes: A population-based cohort study.

AIMS: To compare the risk of osteoarthritis among patients with type 2 diabetes mellitus (T2DM) initiating glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus dipeptidyl peptidase-4 inhibitors (DPP4Is). METHODS: We conducted a nationwide cohort study applying a target trial emulation framework. From the National Health Insurance Service data of South Korea (2010-2022), eligible patients included adult patients with T2DM initiated GLP-1RAs or DPP4Is. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs of incident osteoarthritis, and were weighted using propensity score fine stratification. RESULTS: Among 2,056,824 eligible patients, 9,866 started GLP-1RAs (mean age 45 years; 55% male; 67% dulaglutide) and 2,047,158 started DPP4Is (mean age 56 years; 70% male). After weighting, all covariates were well balanced, with patients having a mean age of 45 years and 55% being male. The incidence rates per 100 person-years for osteoarthritis were 3.99 (95% CI, 3.54-4.48) and 4.36 (4.34-4.38) among GLP-1RAs and DPP4Is users, respectively. Compared to DPP4Is, GLP-1RAs were not associated with a lower risk of osteoarthritis (HR 0.93, 95% CI, 0.83-1.05). CONCLUSIONS: The use of GLP-1RAs, primarily dulaglutide, was not associated with lower risk of osteoarthritis compared with DPP4Is use among patients with T2DM.