SGLT2 Inhibitors Linked to Lower Risk of New-Onset Atopic Dermatitis in People with Type 2 Diabetes

Highlights

– Nationwide Taiwanese cohort study reports lower incidence of new-onset atopic dermatitis (AD) among people with type 2 diabetes who initiated SGLT2 inhibitors versus DPP4 inhibitors (IPTW-adjusted HR 0.847).

– Incidence rates: 9.742 vs 12.070 per 1000 person-years for SGLT2i and DPP4i users, respectively; highest SGLT2i dose associated with greatest reduction (IPTW-adjusted HR 0.647).

– Protective association was consistent across sensitivity analyses and SGLT2i agents, with a stronger effect observed in men.

Background: clinical context and unmet need

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by eczematous lesions, intense pruritus, and a relapsing course. AD prevalence varies by age and geography, but it contributes substantial morbidity, sleep disturbance, and quality-of-life impairment. In adults with multimorbidity, dermatologic disease frequently coexists with metabolic conditions such as type 2 diabetes mellitus (T2DM), raising questions about interplay between glycemic therapies and skin disease risk.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have become core glucose-lowering agents for T2DM because of consistent benefits on cardiorenal outcomes and tolerable safety profiles. Their mechanism—promoting glycosuria and natriuresis—has also been linked to systemic metabolic and anti-inflammatory effects. Conversely, dipeptidyl peptidase-4 inhibitors (DPP4i) have immunomodulatory effects and have been variably associated with dermatologic adverse events such as bullous pemphigoid. Understanding whether commonly prescribed classes differentially influence risk of new-onset AD is relevant for clinical decision-making in patients at elevated dermatologic risk.

Study design and methods

Wen and colleagues conducted a nationwide, active-comparator cohort study using the Taiwan National Health Insurance database (May 2016–December 2018). Adults with T2DM who newly initiated either an SGLT2 inhibitor (n = 148,354) or a DPP4 inhibitor (n = 322,703) were included; persons with prior prescriptions for either class in the preceding 12 months were excluded to capture new-user effects.

The primary outcome was incident atopic dermatitis identified via diagnostic codes in claims data. To address confounding by indication and baseline imbalances, the investigators used inverse probability of treatment weighting (IPTW) derived from propensity scores that included baseline demographics, comorbidities, and medication history. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for new-onset AD comparing SGLT2i versus DPP4i users. The authors also performed sensitivity analyses, subgroup analyses, sex-specific assessments, and dose–response evaluation by SGLT2i exposure intensity.

Key findings

Incidence and primary association

Crude incidence rates of AD were 9.742 per 1000 person-years among SGLT2i users versus 12.070 per 1000 person-years among DPP4i users. After IPTW adjustment, initiation of an SGLT2i was associated with a significantly lower risk of new-onset AD (IPTW-adjusted HR 0.847; 95% CI not reported in the summary but provided in the original article).

Consistency across agents and dose-response

The protective association was observed across different SGLT2 inhibitor agents evaluated, suggesting a potential class effect rather than an idiosyncratic drug-specific signal. The authors report a dose–response relationship: the highest cumulative or intensity category of SGLT2i exposure showed the greatest reduction in AD risk (IPTW-adjusted HR 0.647), strengthening the argument for a potentially causal relationship.

Sex differences and subgroup findings

Sex-specific analyses indicated a larger relative benefit in men (IPTW-adjusted HR 0.750) than in women, an intriguing observation that prompts hypotheses regarding sex differences in immune responses, skin barrier biology, or prescribing patterns. Other subgroup and sensitivity analyses reportedly produced consistent results, supporting robustness.

Safety

The study focused on incident AD as the outcome and did not provide comparative safety profiling beyond that endpoint in the abstract. As an observational claims-based analysis, it was not designed to adjudicate adverse events requiring clinical or laboratory detail beyond diagnostic codes.

Interpretation and biological plausibility

The association between SGLT2i use and reduced incidence of AD may reflect several, non–mutually exclusive mechanisms. SGLT2 inhibitors have been linked to reductions in systemic markers of inflammation and oxidative stress in preclinical and clinical settings, which could theoretically attenuate inflammatory pathways involved in AD pathogenesis. Metabolic improvements (weight loss, improved glycemic variability) could also modulate immune function and skin barrier integrity indirectly.

Conversely, the active comparator choice—DPP4 inhibitors—merits careful consideration. DPP4 (CD26) plays roles in immune regulation, and DPP4i have been associated with autoimmune blistering disorders in some pharmacoepidemiologic studies. If DPP4i increase dermatologic risk, then the observed protective association with SGLT2i may partly reflect an elevated baseline risk in the comparator arm rather than a uniquely protective effect of SGLT2 inhibition. The consistency across agents and the dose–response signal, however, argue that at least a component of the association may be attributable to SGLT2i themselves.

Strengths and limitations

Strengths

– Large, nationwide cohort with new-user, active-comparator design minimizes immortal time bias and some confounding by indication.

– Use of IPTW to balance a broad set of baseline covariates improves comparability between groups.

– Dose–response and multiple sensitivity analyses increase robustness of the findings.

Limitations

– Observational claims data are susceptible to residual confounding from unmeasured factors (e.g., family history of atopy, environmental exposures, body mass index if not captured, smoking status, over-the-counter topical therapy use, or disease severity markers).

– Case ascertainment of AD via diagnostic codes may misclassify disease (sensitivity and specificity depend on coding practices); severity, extent, and histologic confirmation were unavailable.

– Comparator selection (DPP4i) both strengths and weaknesses: while clinically relevant as an active comparator class, DPP4i immunomodulatory properties could bias results if they increase AD risk.

– Generalizability outside Taiwan or to populations with different baseline AD prevalence, genetic backgrounds, or prescribing patterns may be limited.

Expert commentary and clinical implications

For clinicians managing adults with T2DM, these data are hypothesis-generating but not prescriptive. The study suggests that SGLT2 inhibitors may be associated with a lower risk of developing AD compared with DPP4 inhibitors in a large East Asian population. This could be an additional consideration when selecting glucose-lowering therapy for patients with existing atopic diathesis or concerns about dermatologic comorbidity, but it should not be the primary determinant of therapy choice in the absence of randomized evidence.

Key practice points:

• Recognize that the observed association does not establish causality. Shared confounding, channeling bias, or comparator effects are plausible.
• When choosing diabetes therapy, prioritize cardiorenal risk profile, glycemic efficacy, tolerability, comorbid conditions, and patient preferences; dermatologic risk could be a secondary consideration.
• Be vigilant for skin manifestations across glucose-lowering agents; prompt dermatology referral and medication review are warranted when new or severe eruptions appear.

Research implications and next steps

Further work is needed to probe causality and mechanism. Potential next steps include:

• Replication studies in diverse populations with granular clinical data including BMI, smoking, family history of atopy, and dermatologist-confirmed AD diagnoses.
• Mechanistic studies examining the effects of SGLT2 inhibition on cutaneous immune responses, barrier function, and systemic inflammatory mediators relevant to AD.
• Randomized pragmatic trials or nested case–control designs within RCTs that capture dermatologic endpoints, where feasible, to reduce confounding and validate observational signals.

Conclusion

Wen et al. report a robust association between SGLT2 inhibitor initiation and a lower incidence of new-onset atopic dermatitis compared with DPP4 inhibitors in a large Taiwanese cohort. The effect was consistent across sensitivity analyses, present across SGLT2 agents, and showed a dose–response relationship, with a stronger signal in men. While intriguing and hypothesis-generating, the findings require cautious interpretation because of residual confounding, possible comparator-related effects, and limitations inherent to claims-based research. Clinicians should not prescribe SGLT2 inhibitors solely for AD prevention based on current evidence, but the results add to the body of literature on pleiotropic effects of glucose-lowering therapies and suggest directions for translational and clinical research.

Funding and clinicaltrials.gov

This analysis summarises findings reported by Wen et al. (Br J Dermatol. 2025). The original article should be consulted for specific funding disclosures and acknowledgements. As an observational database study, the work was not registered on clinicaltrials.gov as a randomized trial.

References

1. Wen YL, Hsu WT, Chen YH, Kao HH, Liao CC, To SY, Yang HW, Kao LT. Sodium-glucose cotransporter 2 inhibitors and inverse risk of new-onset atopic dermatitis in a cohort with diabetes: a nationwide active-comparator study. Br J Dermatol. 2025 Jun 20;193(1):74-84. doi: 10.1093/bjd/ljaf086. PMID: 40037684.

2. American Diabetes Association. Standards of Medical Care in Diabetes—2024. Diabetes Care. 2024;47(Suppl 1):S1–S276.

3. Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL, Berger TG, Bergman JN, Cohen DE, Cooper KD, et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70(2):338-351.

Author note

This article is a critical, evidence-based interpretation of the cited cohort study intended for clinicians and health professionals. For clinical decisions, refer to the original publication and clinical guidelines.