Sodium-glucose cotransporter 2 inhibitors and inverse risk of new-onset atopic dermatitis in a cohort with diabetes: a nationwide active-comparator study.

Abstract

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i), a novel class of antidiabetic medication, have emerged as a key treatment option in diabetes management. Notably, SGLT2i promote glucose and sodium excretion through urine, a mechanism that may be implicated in the potential association between SGLT2i use and risk of atopic dermatitis (AD).

Objectives: To investigate the relationship between SGLT2i use and new-onset AD in people with diabetes.

Methods: This nationwide active-comparator cohort study used data from the Taiwan National Health Insurance database to investigate the association between SGLT2i use and AD risk. The study included adults with type 2 diabetes mellitus who initiated SGLT2i or DPP4i between May 2016 and December 2018, with no prescriptions for other SGLT2i or DPP4i in the 12 months prior to cohort entry. A total of 148 354 SGLT2i users were identified as the study group, while 322 703 DPP4i users were designated as the active comparator group. The primary outcome was the incidence of AD. To minimize potential confounding, inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics, medical history and ever having used medication between the two groups. Additionally, sensitivity analyses, subgroup analyses and sex-specific assessments were conducted to further validate the findings. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of developing AD.

Results: SGLT2i users had a lower incidence of AD (9.742 vs. 12.070 per 1000 PY) than DPP4i users. SGLT2i users had a significantly lower risk of AD compared with DPP4i users (HR 0.847) after IPTW adjustment. Different types of SGLT2i also showed a consistent protective effect for AD. Notably, the highest SGLT2i dosage was associated with the lowest risk of AD (IPTW-adjusted HR 0.647), consistent across sensitivity analyses. Additionally, men who use SGLT2i exhibited a much lower risk of AD (IPTW-adjusted HR 0.750) than women who use SGLT2i.

Conclusions: SGLT2i show a significant protective effect against AD in patients with diabetes compared with DPP4i. This robust finding, consistent across weighting and sensitivity analyses, supports SGLT2i use, with a strong protective effect also found in the dose-response analysis.