Skin-related effects of GLP-1 receptor agonists vs DPP-4 inhibitors in T2DM

Overview

This large real-world study emulating a clinical trial found that GLP-1 receptor agonists (GLP-1 RAs) in type 2 diabetes patients were associated with a higher risk of psoriasis but a lower risk of autoimmune blistering diseases such as pemphigus and bullous pemphigoid compared to dipeptidyl peptidase-4 inhibitors (DPP-4is). These findings persisted over up to 4 years of follow-up and across multiple analyses.

Background

Incretin-based therapies, including GLP-1 receptor agonists and DPP-4 inhibitors, are key treatments for type 2 diabetes mellitus (T2DM) that improve glycemic control through different mechanisms. GLP-1 RAs also have anti-inflammatory and immunomodulatory effects, which may influence autoimmune and inflammatory skin diseases. DPP-4 inhibitors have been linked to increased risks of autoimmune blistering skin diseases, but the dermatologic safety profile of GLP-1 RAs remains less well characterized. Comparative data on skin-related outcomes between these two drug classes are clinically important for guiding therapy selection.

Data Highlights

Key Findings

• GLP-1 RA initiation was associated with a 19% increased risk of incident psoriasis compared to DPP-4i initiation.
• GLP-1 RA use was linked to a 68% lower risk of pemphigus relative to DPP-4i use.
• Risk of bullous pemphigoid was reduced by 39% among GLP-1 RA users compared to DPP-4i users.
• No significant differences were found for other autoimmune or inflammatory skin diseases after correcting for multiple testing.
• Results were consistent across subgroup and sensitivity analyses, supporting robustness.

Clinical Implications

Clinicians should consider the differential dermatologic risk profiles when selecting incretin-based therapies for patients with type 2 diabetes. While GLP-1 RAs may increase psoriasis risk, they appear safer than DPP-4is regarding autoimmune blistering diseases. Ongoing skin monitoring is advisable during therapy to detect and manage potential skin-related adverse effects.

Conclusion

This comprehensive trial emulation study provides important comparative safety data indicating that GLP-1 receptor agonists have distinct skin-related effects compared to DPP-4 inhibitors, with increased psoriasis risk but decreased autoimmune blistering disease risk. These findings can inform personalized treatment decisions and highlight the need for dermatologic vigilance.

References

1. TriNetX US Collaborative Network Study 2023 -- Skin-related effects of GLP-1 RAs vs DPP-4is in T2DM