GLP-1 receptor agonist initiation and newly recorded ankylosing spondylitis diagnoses in type 2 diabetes: a target trial emulation

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have broad cardiometabolic benefits, but their comparative association with ankylosing spondylitis diagnoses is uncertain. We emulated a target trial in the TriNetX US Collaborative Network among adults with type 2 diabetes who initiated GLP-1 RAs or dipeptidyl peptidase-4 inhibitors between 2018 and 2022. The new-user, active-comparator design used 1:1 propensity score matching and Cox models; the Benjamini–Hochberg false discovery rate (FDR) procedure covered six outcomes. After matching, 208,970 patients (104,485 per group) were included. GLP-1 RA initiation was associated with more newly recorded ankylosing spondylitis diagnoses (0.15% vs. 0.10%; hazard ratio, 1.49; 95% confidence interval, 1.16–1.91; P = 0.001). Polyosteoarthritis showed a nominal association (1.80% vs. 1.73%; hazard ratio, 1.07; 95% confidence interval, 1.01–1.15; P = 0.031) that was not significant after FDR adjustment (P = 0.093); rheumatoid arthritis, other rheumatoid arthritis, gout, and Sjögren’s syndrome did not differ. The primary association was directionally consistent across prespecified sensitivity analyses. These findings identify a potential comparative safety signal that warrants independent confirmation.