DPP-4i linked to lower psoriasis risk but higher dermatomyositis risk compared to GLP-1RA in type 2 diabetes patients

The management of Type 2 Diabetes has expanded significantly with the introduction of novel antidiabetic agents, including glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP-4i), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). While these drugs offer substantial glycemic control and cardiovascular benefits, their comparative immunologic safety profiles, particularly concerning the incidence of autoimmune diseases, remain largely uncharacterized. Understanding these differential risks is crucial for optimizing drug selection, especially in patients with existing autoimmune predispositions or those at higher risk.

Researchers conducted emulated target trials utilizing electronic health record data from 152 healthcare organizations within the TriNetX network, spanning 2016-2023. The study included adults with Type 2 Diabetes initiating monotherapy with DPP-4i, GLP-1RA, or SGLT2i, with no prior history of autoimmune disease. Propensity score matching was employed to balance demographics, comorbidities, laboratory data, and concurrent medications across cohorts. The primary outcomes assessed were the three-year risks of incident autoimmune diseases, including psoriasis, rheumatoid arthritis, systemic sclerosis, dermatomyositis, and multiple sclerosis. Cohorts comprised 118,419 matched DPP-4i versus GLP-1RA pairs, 102,810 DPP-4i versus SGLT2i pairs, and 105,869 GLP-1RA versus SGLT2i pairs.

Compared with GLP-1RA treatment, DPP-4i use demonstrated a significantly lower risk for several autoimmune conditions. Specifically, DPP-4i was associated with a reduced risk of psoriasis (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.70-0.85), psoriatic arthritis (HR 0.65, 95% CI 0.53-0.79), and autoimmune thyroiditis (HR 0.68, 95% CI 0.59-0.76). Conversely, DPP-4i treatment was linked to an increased risk for other specific autoimmune diseases.

DPP-4i use was associated with a higher risk of dermatomyositis (HR 2.18, 95% CI 1.24-3.53) and bullous pemphigoid (HR 1.78, 95% CI 1.24-2.46) compared to GLP-1RA. The conclusion also noted an increased risk for giant cell arteritis with DPP-4i compared to GLP-1RA, though specific HRs were not detailed in the results section of the abstract. Importantly, no significant differences in autoimmune disease incidence were observed when comparing GLP-1RA and SGLT2i treatments.