A target trial emulation found that adults with type 2 diabetes who initiated glucagon-like peptide-1 receptor agonists had more newly recorded ankylosing spondylitis diagnoses than comparable patients initiating dipeptidyl peptidase-4 inhibitors. The study used data from the TriNetX US Collaborative Network and included 208,970 matched patients, with 104,485 in each treatment group. The researchers emulated a target trial using a new-user, active-comparator design.
Adults with type 2 diabetes initiated either GLP-1 receptor agonists or dipeptidyl peptidase-4 inhibitors between 2018 and 2022. The groups were matched at a 1:1 ratio with propensity score methods, and the analysis used Cox models to estimate associations over time. The Benjamini–Hochberg false discovery rate procedure covered six evaluated outcomes.
Newly recorded ankylosing spondylitis diagnoses occurred in 0.15% of patients initiating GLP-1 receptor agonists and 0.10% of those initiating dipeptidyl peptidase-4 inhibitors. The estimated hazard ratio was 1.49, with a 95% confidence interval of 1.16–1.91 and a P value of 0.001. The primary association was directionally consistent across prespecified sensitivity analyses, according to the study abstract.
Polyosteoarthritis showed a nominal association with GLP-1 receptor agonist initiation: diagnoses were recorded in 1.80% of the GLP-1 receptor agonist group and 1.73% of the comparator group, with a hazard ratio of 1.07 and a 95% confidence interval of 1.01–1.15. Its unadjusted P value was 0.031, but the association was not significant after false discovery rate adjustment, for which the adjusted P value was 0.093. Rheumatoid arthritis, other rheumatoid arthritis, gout and Sjögren’s syndrome did not differ significantly between the groups.
The authors characterized the ankylosing spondylitis finding as a potential comparative safety signal that warrants independent confirmation. The result identifies a signal for further investigation rather than a definitive clinical conclusion.
Subject of Research: Comparative safety associations of GLP-1 receptor agonists and newly recorded ankylosing spondylitis diagnoses in adults with type 2 diabetes
Article Title: GLP-1 receptor agonist initiation and newly recorded ankylosing spondylitis diagnoses in type 2 diabetes: a target trial emulation
Article References: Lu, Y.-C., Li, T.-H., Liu, Y.-F., & Tsai, M.-H. (2026). GLP-1 receptor agonist initiation and newly recorded ankylosing spondylitis diagnoses in type 2 diabetes: a target trial emulation. Scientific Reports. https://doi.org/10.1038/s41598-026-75731-6
Image Credits: AI Generated
DOI: 10.1038/s41598-026-75731-6
Keywords: GLP-1 receptor agonists, ankylosing spondylitis, type 2 diabetes, DPP-4 inhibitors, target trial emulation, observational study, drug safety, TriNetX, propensity score matching, hazard ratio, GLP-1, receptor
