BOSTON — Jeffrey A. Sparks, MD, MMSc, of Harvard Medical School and Brigham and Women's Hospital in Boston, and colleagues published a report in ACR Open Rheumatology. The study analyzed the TriNetX database of patient records to examine associations between DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2 inhibitors, and new diagnoses of autoimmune conditions.

The researchers generated pairwise matches of patients receiving different medication types using target trial emulation methodology. The study included more than 100,000 pairs of patients in each of three comparisons: DPP-4 inhibitors versus GLP-1 agonists, DPP-4 inhibitors versus SGLT-2 inhibitors, and GLP-1 agonists versus SGLT-2 inhibitors.

Compared with GLP-1 agonists, DPP-4 inhibitors were associated with less risk for plaque psoriasis, with a hazard ratio (HR) of 0.79 (95% CI 0.70-0.85). DPP-4 inhibitors also showed less risk for psoriatic arthritis (HR 0.65, 95% CI 0.53-0.79) and autoimmune thyroiditis (HR 0.68, 95% CI 0.59-0.76) when compared to GLP-1 agonists.

Conversely, DPP-4 inhibitors were associated with more risk for bullous pemphigoid (HR 1.78, 95% CI 1.24-2.46) and dermatomyositis (HR 2.18, 95% CI 1.24-3.53) compared to GLP-1 agonists. Against SGLT-2 inhibitors, DPP-4 inhibitors were associated with a doubled risk for bullous pemphigoid (HR 2.07, 95% CI 1.34-3.05) and dermatomyositis (HR 2.03, 95% CI 1.35-3.02), and an increased risk for giant cell arteritis (HR 1.83, 95% CI 1.31-2.65).

DPP-4 inhibitors were associated with less risk for psoriasis (HR 0.81, 95% CI 0.70-0.91) and autoimmune thyroiditis (HR 0.76, 95% CI 0.63-0.90) when compared with SGLT-2 inhibitors. No differences were observed between GLP-1 drugs and SGLT-2 inhibitors for any of the 19 autoimmune conditions examined. The study found no differences between drug classes for rheumatoid arthritis, lupus, inflammatory bowel disease, multiple sclerosis, celiac disease, or systemic sclerosis.

The researchers analyzed incidence of non-autoimmune diagnoses such as hand lacerations and inguinal hernia as negative controls. No differences were observed between medication classes in this analysis. The researchers adjusted for factors including baseline HbA1c, body mass index, tobacco and alcohol use, and renal function. The study did not include a control group of patients receiving older medications such as metformin or sulfonylureas, or no medication.

Sparks stated that the study's findings do not establish mechanistic certainty and should be regarded as preliminary signals. He added that future work incorporating mechanistic endpoints and external untreated comparators is essential to further elucidate the degree to which relative differences may translate to clinically relevant impacts.