Association between autoimmune diseases and glucagon-like peptide-1 receptor agonists: A real-world evidence study

🥉 Top 5% JournalJun 22, 2025Journal of autoimmunity

Links between autoimmune diseases and drugs that activate the glucagon-like peptide-1 receptor

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Abstract

Patients using GLP-1 receptor agonists have a 30% higher risk of developing autoimmune thyroiditis compared to those using DPP-4 inhibitors.

GLP-1 receptor agonists are associated with increased risks of autoimmune conditions such as ulcerative colitis, rheumatoid arthritis, and psoriasis.
The risk of autoimmune thyroiditis is notably higher among GLP-1 RA users, with a hazard ratio of 1.30.
Ankylosing spondylitis is also linked to GLP-1 RA use, showing a hazard ratio of 1.30.
Sensitivity analyses support a consistent association between GLP-1 RAs and the incidence of autoimmune diseases.
The findings indicate the need for careful monitoring of patients on GLP-1 receptor agonists.

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INTRODUCTION: The therapeutic advantages of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in diabetes management have been demonstrated. However, their potential association with autoimmune diseases remains unknown. Using a comprehensive real-world dataset, this study compared GLP-1 RAs against dipeptidyl peptidase-4 inhibitors (DPP-4is) with respect to the incidence of autoimmune diseases.

METHODS: This retrospective cohort study, with an active-comparator and new-user design, analyzed data from the TriNetX US Collaborative Network. We identified 4,841,560 patients aged over 18 years with type 2 diabetes from 1 January 2015 to 31 December 2022. Finally, 412,021 and 383,415 patients were included in the GLP-1 RAs and DPP-4is groups, respectively. Propensity score matching was used to balance baseline characteristics, and hazard ratios (HRs) were estimated with Cox regression models over an eight-year follow-up.

RESULTS: After propensity score matching, each group included 290,770 patients. The analysis revealed that patients receiving GLP-1 RAs exhibited significantly higher risks of certain autoimmune conditions, including ulcerative colitis (HR, 1.11; 95 % CI, 1.04-1.19), rheumatoid arthritis (HR, 1.08; 95 % CI, 1.03-1.12), autoimmune thyroiditis (HR, 1.30; 95 % CI, 1.24-1.38), ankylosing spondylitis (HR, 1.30; 95 % CI, 1.13-1.51), and psoriasis (HR, 1.17; 95 % CI, 1.12-1.22), compared to those on DPP-4is. Moreover, sensitivity analyses consistently revealed a significant link between GLP-1 RAs use and autoimmune diseases.

CONCLUSIONS: This study suggests that compared with DPP-4is, the use of GLP-1 RAs is linked to increased risks of certain autoimmune diseases. Careful monitoring might be required among patients on GLP-1 RAs.

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