Can dipeptidyl peptidase-4 inhibitors reduce the risk of autoimmune disease?

The authors evaluated the risk of autoimmune disease development in patients starting a dipeptidyl peptidase inhibitor for type 2 diabetes.

Dipeptidyl peptidase-4 (DPP4) is a protein that plays a major role in glucose metabolism. DPP4-inhbitors such as linagliptin (Tradjenta), saxagliptin (Onglyza) and sitagliptin (Januvia) are used alone or in conjunction with other drugs as oral glucose-lowering drugs in type 2 diabetes. However, DPP4 is expressed on many cells, including T-lymphocytes and macrophages, cells of the immune system. To date, the effect of DPP4 inhibitors on the immune system, particularly on autoimmune disorders (disorders in which the immune system becomes overactive and attacks healthy body tissue)  is not well known.

The objective of this study was to estimate the risk of autoimmune disease in patients starting a DPP4-inhbitor drug compared to patients starting a non-DPP4 inhibitor oral hypoglycemic (glucose-lowering) agent.  

Thestudy evaluated commercial insurance-claims data from 73,928 patients who had at least one dispensing for a DPP4 inhibitor during the study period and 163,062 patients who had at least one dispensing for a non-DPP4 inhibitor drug during the study period. The average follow-up was 0.74 years for those taking DPP4 inhibitors and 0.72 years for those taking non-DPP4 inhibitors. Outcomes of interest were development of rheumatoid arthritis (painful inflammation of the joints) or other autoimmune diseases such as systemic lupus erythematosus (the body mistakenly attacks healthy tissue in the skin, joints, kidneys brain and other organs), psoriasis (skin disease marked by red, itchy, scaly patches), psoriatic arthritis (arthritis associated with psoriasis), multiple sclerosis (damage to nerve cells in the brain and spinal cord) and inflammatory bowel disease (inflammatory conditions in the colon and small intestine).

Overall, there were 179 patients diagnosed with rheumatoid arthritis, 249 with other autoimmune disease and 424 with composite (overall) autoimmune disease after the initiation of either therapy.

The risk of rheumatoid arthritis within 365 days of follow-up was reduced by 34% in patients taking DPP4 inhibitors compared to those taking non-DPP4 inhibitors. The risk of other autoimmune disease within the same period was reduced by 27% in those taking DPP4 inhibitors compared to those taking non-DPP4 inhibitors. The risk of composite (all) autoimmune disease was reduced by 32% in those taking DPP4 inhibitors compared to those taking non-DPP4 inhibitors.

The risk of composite autoimmune disease was also deemed to be reduced by 47% for those taking DPP4 inhibitors compared to patients taking sulfonylureas (glimepiride;Amaryl, glipizide;Glucotrol).

The authors concluded that initiation of DPP4 inhibition therapy was associated with a decreased risk of autoimmune disease compared to non-DPP4 initiation therapy. 

The 12-month follow up may not have been long enough to account for all potential confounders.