Dermatologic outcomes associated with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a large-scale target trial emulation
By
Yi-Lun Chiang
Tzu-Hao Li
Yu-Wei Fang
Ya-Fang Liu
Jennifer Wu
Ming-Hsien Tsai
April 13, 2026
Clinical Scorecard: Skin-related effects of glucagon-like peptide-1 receptor agonists in individuals with type 2 diabetes: findings from a comprehensive trial emulation
At a Glance
Category Detail
Condition Autoimmune and inflammatory skin diseases in type 2 diabetes patients Key Mechanisms GLP-1 RAs modulate incretin pathway enhancing insulin secretion, suppress glucagon, promote satiety, and exert anti-inflammatory and immunomodulatory effects; DPP-4is inhibit dipeptidyl peptidase-4 affecting immune pathways Target Population Adults with type 2 diabetes initiating GLP-1 receptor agonists or DPP-4 inhibitors Care Setting Real-world clinical settings using electronic health record data from US healthcare organizations
Key Highlights
GLP-1 RA initiation is associated with increased risk of incident psoriasis compared to DPP-4i initiation (HR 1.19). GLP-1 RA initiation is linked to decreased risks of pemphigus (HR 0.32) and bullous pemphigoid (HR 0.61) relative to DPP-4is. No significant differences were found for other autoimmune or inflammatory skin diseases after multiple-testing correction. Guideline-Based Recommendations
Diagnosis
Monitor for new onset autoimmune or inflammatory skin diseases in patients initiating incretin-based therapies. Exclude outcomes occurring within 3 months of drug initiation to reduce protopathic bias. Management
Consider dermatologic safety profiles when selecting between GLP-1 RAs and DPP-4is for T2DM treatment. Recognize GLP-1 RAs may increase psoriasis risk but reduce autoimmune blistering diseases compared to DPP-4is. Monitoring & Follow-up
Implement ongoing skin monitoring during up to 4 years of follow-up for patients on GLP-1 RAs or DPP-4is. Be vigilant for signs of psoriasis and autoimmune blistering diseases in this population. Risks
GLP-1 RAs carry a higher risk of psoriasis compared to DPP-4is. DPP-4is are associated with increased risk of autoimmune blistering diseases such as bullous pemphigoid. Patient & Prescribing Data
Adults with type 2 diabetes initiating GLP-1 receptor agonists or DPP-4 inhibitors without prior use of either class
GLP-1 RAs offer cardiovascular and renal benefits and have distinct dermatologic safety profiles compared to DPP-4is, necessitating individualized therapy selection considering skin disease risks.
Clinical Best Practices
Use propensity score matching and active-comparator new-user designs to evaluate real-world drug safety. Exclude early events post-treatment initiation to minimize protopathic bias in observational studies. Balance metabolic benefits of GLP-1 RAs with potential increased psoriasis risk when prescribing. Consider DPP-4i-associated risks of autoimmune blistering diseases in treatment decisions. Maintain long-term dermatologic surveillance in patients receiving incretin-based therapies. References
