(A-107) Glucagon-like Peptide-1 Receptor Agonists and Reduced Risk of New-Onset Atopic Dermatitis in Patients with Type 2 Diabetes: A Nationwide, Active-Comparator Study

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by immune dysregulation, barrier dysfunction, and oxidative stress. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated anti-inflammatory properties by reducing oxidative stress, inhibiting NF-κB activation, suppressing TNF-α, and increasing nitric oxide production. However, the association between GLP-1RAs and the risk of AD remains unclear.

Objectives: To investigate the association between GLP-1RAs use and the risk of new-onset AD in patients with type 2 diabetes.

Methods: This nationwide, active-comparator cohort study utilized data from the Taiwan National Health Insurance Database. The study included adult patients with type 2 diabetes who initiated GLP-1RAs or dipeptidyl peptidase-4 inhibitors (DPP4i) between May 2016 and December 2018, with no prior prescriptions for these medications in the 12 months before cohort entry. A total of 17,904 GLP-1RA users comprised the study group, while 362,671 DPP4i users served as the primary active comparator group. Additionally, a secondary comparator group was established with 19,092 GLP-1RA users and 442,866 metformin users to assess potential biases between groups. The primary outcome was the incidence of new-onset AD. To account for baseline differences in demographics, medical history, and prior medication use, inverse probability of treatment weighting (IPTW) was applied. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: The incidence of AD was significantly lower in the GLP-1RA group than in the DPP4i group (9.58 vs. 11.30 per 1,000 person-years). After IPTW adjustment, GLP-1RA use remained protective (IPTW crude HR = 0.877) and this association remained robust after adjusting for covariates (IPTW-adjusted HR = 0.871). When compared with metformin users, GLP-1RA treatment was also associated with a lower risk of AD (9.71 vs. 10.97 per 1,000 person-years). The IPTW crude HR was 0.992, and the association persisted after adjustment (IPTW-adjusted HR = 0.976).

Conclusions: This nationwide cohort study demonstrated that GLP-1RAs are associated with a reduced risk of new-onset AD in patients with type 2 diabetes, irrespective of whether DPP4i or metformin users were used as comparators. The robust and consistent findings across multiple weighting analyses further support the protective role of GLP-1RAs in mitigating AD risk. Future studies should explore the mechanistic pathways underlying this association and its clinical implications for inflammatory disease management.