Dipeptidyl Peptidase-4 Inhibitors Associated with Lower Psoriatic Disease Risk in Type 2 Diabetes: A 13-Year Nationwide Cohort Study with Mechanistic Validation

Psoriatic disease, encompassing psoriasis and -psoriatic arthritis, is a chronic inflammatory condition with bidirectional associations with type 2 diabetes mellitus. Current evidence regarding dipeptidyl peptidase-4 inhibitors' effects on psoriatic disease presents conflicting findings, with the impact on psoriatic arthritis remaining unexplored. This study aimed to investigate the association between dipeptidyl peptidase-4 inhibitors use and psoriatic disease risk in diabetic patients. A nationwide population-based cohort study was conducted using Taiwan's National Health Insurance Research Database (2009-2021), including 78,865 patients with type 2 diabetes mellitus: 15,773 dipeptidyl peptidase-4 inhibitors users and 63,092 matched controls. Primary outcomes were incident psoriasis and psoriatic arthritis. During a median follow-up of 7.08 years, 393 cases developed psoriatic disease: 51 cases in the dipeptidyl peptidase-4 inhibitors cohort vs 342 cases in controls. Dipeptidyl peptidase-4 inhibitors therapy was associated with significantly lower psoriatic disease risk (adjusted hazard ratio 0.583, 95% confidence interval 0.430-0.696). Individual dipeptidyl peptidase-4 inhibitors demonstrated varying protective effects, with alogliptin showing the strongest protection. In vitro experiments confirmed that dipeptidyl peptidase-4 inhibitors significantly attenuated inflammatory responses in human skin cells. This large-scale nationwide study demonstrates that dipeptidyl peptidase-4 inhibitors use is associated with a 41.7% lower risk in psoriatic disease in diabetic patients.