November 6, 2013
DPP-4 Inhibitors Could Play Role in Thwarting
Autoimmune Disease

San Diego, CA—While dipeptidyl peptidase-4 (DPP-4) inhibitors have shown effectiveness in controlling blood sugar in patients with type 2 diabetes, they may have another benefit according to recent research: reducing the risk of autoimmune diseases.

The research was presented recently at the American College of Rheumatology Annual Meeting in San Diego.

For the study, researchers compared patients taking DPP-4 inhibitors—linagliptin (Tradjenta), saxagliptin (Onglza), and sitagliptin (Januvia)—with those not using the therapies, assessing how often they developed autoimmune diseases such as rheumatoid arthritis, lupus, inflammatory bowel disease, psoriasis, and multiple sclerosis.

“DPP-4 is a transmembrane glycoprotein widely expressed in various cells and is also involved in the immune system,” said lead investigator Seoyoung C. Kim, MD, assistant professor of medicine at Brigham and Women’s Hospital in Boston. “Prior studies suggested a potential role of DPP4i as a novel therapy for several inflammatory diseases by inhibiting T-cell proliferation and cytokine production. Our hypothesis was that patients with type 2 diabetes starting a DPP4i would have a reduced risk of incident RA and other autoimmune diseases compared to those patients starting non-DPP4i hypoglycemic agents.”

For the study, researchers used data from U.S. commercial insurance claims from 2005 to 2011, comparing 58,275 patients 40-years-old or older with type 2 diabetes starting DPP4i combination therapy against similar subjects with type 2 diabetes who started non-DPP4i combination therapy.

The study excluded patients taking insulin, as well as those with pre-existing systemic autoimmune diseases, HIV, or cancer.

To determine development of autoimmune diseases, the study looked at two or more diagnosis codes that were 7 or more days apart and one or more prescriptions for disease-specific immunosuppressive drugs or steroids. The analysis controlled for potential confounders such as age, sex, co-existing conditions, diabetes-related factors, medications, and healthcare utilization.

Study results indicated that patients with type 2 diabetes who were starting a DPP-4 inhibitor were at a lower risk of developing autoimmune diseases compared to those starting non-DPP4i drugs. The overall incidence rate of autoimmune diseases was low at about one in a 1,000, but patients on DPP4i combination therapy still appeared to be 34% less likely to develop rheumatoid arthritis and 27% less likely to develop the other autoimmune diseases.

When DPP4i was compared to sulfonylureas in a subgroup analysis, a similarly protective effect was evident, although that was not the case when comparing DPP4i with thiazolidinediones.

“Among patients with type 2 diabetes, initiating DPP4i combination therapy may be associated with a decreased risk of rheumatoid arthritis or other autoimmune diseases compared to initiating non-DPP4i combination therapy,” Kim noted.

“Although our results are not definitive, these results may contribute to the understanding of new mechanistic pathways for preventing or delaying the onset of autoimmune diseases. It could also lead to a potential new therapeutic approach. Future research is needed to determine the effect and safety of DPP4i in the non-diabetic population.”

U.S. Pharmacist Social Connect