Glucagon-like peptide-1 receptor agonists mitigate the risk of major adverse cardiovascular events in patients with atopic dermatitis and type 2 diabetes

Summary: Purpose: Atopic dermatitis(AD) has been linked to adverse cardiovascular events, with severe AD conferring a higher risk. However, the effect of cardioprotective medications like glucagon-like peptide-1 receptor agonists (GLP-1RA) in patients with AD remains unclear. Methods: For this retrospective cohort study, the TriNetX database was used to identify adults with type 2 diabetes(T2D), including a subgroup who were treated with GLP-1RA. Patients with AD were propensity-score matched to controls without AD. Outcomes included major adverse cardiovascular events(MACE), myocardial infarction(MI), heart failure(HF), and stroke within 10 years. Cox proportional hazard models were used to assess the effect of AD on outcomes over time. Interaction analyses evaluated whether GLP-1RA mitigated the disease burden of AD on the pre-specified outcomes. Results: After matching, 80,183 pairs of patients with T2D and AD and controls without AD were included. Among them, there were 2,840 pairs of GLP-1RA-treated T2D patients with AD and non-AD controls. Patients with both T2D and AD had a significantly higher risk of MI(HR 1.08; 95%CI 1.03-1.13; P=0.001), HF(HR 1.18; 95%CI 1.15-1.22; P=0.0001), and stroke(HR 1.11; 95%CI 1.07-1.15; P=0.0001) than did T2D controls without AD. GLP-1RA-treated patients with AD and T2D had a significantly lower risk of MACE (HR 0.74; 95%CI 0.60-0.90; P=0.0088) compared to non-AD T2D controls. Interaction analyses showed that GLP-1RA effectively mitigated the risk of MACE (P=0.0024), MI (P=0.036), and stroke (P=0.01) that were associated with AD. Conclusions: In patients with T2D and AD, treatment with GLP1-RA significantly mitigated the risk of new-onset MACE, MI, and stroke compared to non-AD T2D controls, suggesting a potential interplay between AD immune mechanisms and the efficacy of GLP-1RA. Prospective studies are needed to confirm whether pre-existing AD serves as a predictive biomarker for GLP-1RA efficacy. Natalie Braun^{1, 2}, Claire Lin^{1, 2}, Natalie Baker^{1, 2}, Ghida El-Banna^{1, 2}, Bryan L. Peacker^{1, 2}, Kevin Ma^{1, 2}, Steven Chen^{1, 2} 1. Department of Dermatology, Massachusetts General Hospital, Boston, MA, United States. 2. Harvard Medical School, Boston, MA, United States. Clinical Research: Epidemiology and Observational Research