PATIENTS with type 2 diabetes treated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may face an increased risk of developing certain autoimmune diseases compared with those on dipeptidyl peptidase-4 inhibitors (DPP-4is), according to new real-world evidence from a large U.S. cohort.
This retrospective cohort study analyzed data from over 4.8 million adults with type 2 diabetes collected from the TriNetX US Collaborative Network between 2015 and 2022. Researchers included 412,021 patients in the GLP-1 RA group and 383,415 in the DPP-4i group. After applying propensity score matching, each group consisted of 290,770 patients with balanced baseline characteristics. The study used Cox regression modeling to compare the incidence of autoimmune diseases over an eight-year follow-up period.
The findings revealed significantly elevated hazard ratios for several autoimmune conditions in patients taking GLP-1 RAs. These included ulcerative colitis (HR 1.11), rheumatoid arthritis (HR 1.08), autoimmune thyroiditis (HR 1.30), ankylosing spondylitis (HR 1.30), and psoriasis (HR 1.17) when compared with those receiving DPP-4is. Sensitivity analyses supported the robustness of the association between GLP-1 RA use and autoimmune disease risk.
While GLP-1 RAs offer known glycemic and cardiometabolic benefits, these findings raise important questions about immune-related safety profiles. The authors suggest that closer monitoring may be warranted for patients prescribed GLP-1 RAs, particularly those with personal or family histories of autoimmune disease.
This study adds a new dimension to the risk-benefit assessment of GLP-1 RAs, highlighting the importance of long-term pharmacovigilance in diabetes care.
Reference:
Lee YJ et al. Association between autoimmune diseases and glucagon-like peptide-1 receptor agonists: A real-world evidence study. J Autoimmun. 2025;155:103453. [Online ahead of print]
