• GLP-1 receptor agonists for diabetes increased the risk for psoriasis and psoriatic arthritis vs. dipeptidyl peptidase-4 inhibitors.
• GLP-1s were associated with reduced risk for dermatomyositis vs. DPP-4i.

Patients who were prescribed GLP-1 receptor agonists for type 2 diabetes demonstrated increased risks for psoriatic arthritis, psoriasis and autoimmune thyroiditis vs. those treated with dipeptidyl peptidase-4 inhibitors, according to data.

However, the researchers, who published their findings in ACR Open Rheumatology, additionally found that GLP-1 drugs for diabetes were associated with lower risks for dermatomyositis and bullous pemphigoid, compared with dipeptidyl peptidase-4 (DPP-4) inhibition.

“As GLP-1 receptor agonists and other antidiabetic agents become more widely used, understanding their immunologic safety has become increasingly important,” Arjun Mahajan, MS, of Harvard Medical School and Brigham and Women’s Hospital, told Healio. “As one example, weight loss from GLP-1 receptor agonists could be associated with a lower risk for developing certain autoimmune diseases. Thus, we sought to better characterize the comparative risks for incident autoimmune diseases across these major drug classes.”

In the current study, Mahajan and colleagues gathered electronic health record data for patients with type 2 diabetes from 152 health care organizations in the TriNetX federated health research network. The aim was to assess the immunologic safety of DPP-4 inhibitors, GLP-1 receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors as monotherapy. Individuals with no prior autoimmune disease were included.

Three-year incidence autoimmune disease served as the primary endpoint. Autoimmune diseases assessed included systemic lupus erythematosus, cutaneous lupus erythematosus, rheumatoid arthritis, psoriasis, psoriatic arthritis, multiple sclerosis, inflammatory bowel disease, antineutrophilic cytoplasmic antibody-associated vasculitis, giant cell arteritis, dermatomyositis, systemic sclerosis, celiac disease, autoimmune thyroiditis, myasthenia gravis, pemphigus, bullous pemphigoid, polymyositis and polymyalgia rheumatica.

Results showed that compared with GLP-1 receptor agonists, DPP-4 inhibitors were associated with lower risks for psoriasis (HR = 0.79; 95% CI, 0.7-0.85), PsA (HR = 0.65; 95% CI 0.53-0.79), and autoimmune thyroiditis (HR = 0.68; 95% CI, 0.59-0.76).

Meanwhile, DPP-4 inhibitors were associated with higher risks for dermatomyositis (HR = 2.18; 95% CI 1.24-3.53) and bullous pemphigoid (HR = 1.78; 95% CI, 1.24-2.46), compared with GLP-1 receptor agonists.

“Our findings suggest that antidiabetic drug classes may be differentially associated with incident autoimmune disease risk, highlighting the importance of considering immunologic effects alongside established metabolic benefits,” study co-author Jeffrey A. Sparks, MD, MMSc, of Brigham and Women’s Hospital, , told Healio. “For example, both GLP-1 receptor agonists and SGLT-2 inhibitors were associated with a lower risk for bullous pemphigoid compared with DPP-4 inhibitors. We hope these results encourage future mechanistic studies and prospective trials to further elucidate the observed associations.”

Jeffrey A. Sparks, MD, MMSc, can be reached at jsparks@bwh.harvard.edu.

Arjun Mahajan, MS, can be reached at amahajan@hms.harvard.edu.