Rheumatology Xagena

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Autoimmune diseases risk may be reduced by dipeptidyl peptidase-4 inhibitors in type 2 diabetes patients

Dipeptidyl peptidase-4 inhibitors ( DPP4i ), such as Linagliptin, Saxagliptin, and Sitagliptin, are oral glucose-lowering drugs for type 2 diabetes mellitus ( T2DM ). DPP4 is a transmembrane glycoprotein widely expressed in various cells including fibroblasts, T lymphocytes, and macrophages, and has a co-stimulatory function in the immune response. Altered levels of DPP4 activity were noted in patients with autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus , inflammatory bowel disease, psoriasis, and multiple sclerosis.

The objective of a study was to estimate the incidence rate of systemic autoimmune diseases in patients with type 2 diabetes mellitus initiating a DPP-4 inhibitor compared to those initiating non-DPP4i oral hypoglycemic agents.

Researchers, at Brigham and Women's Hospital ( Boston, US ), conducted a population-based cohort study using commercial insurance claims data ( 2005-2011 ). Among patients aged greater than or equal to 40 years with type 2 diabetes mellitus, two mutually exclusive exposure groups were selected: 1) DPP4i combination therapy ( DPP4i and at least 1 other oral non-DPP4i drugs ) and 2) non-DPP4i combination therapy ( 2 or more oral non-DPP4i drugs ).

Patients with a diagnosis of systemic autoimmune disease, HIV, and cancer, and use of Insulin-containing drugs or immunosuppressive drugs at baseline were excluded.

Rheumatoid arthritis and other autoimmune diseases were defined with greater than or equal to 2 diagnosis codes that were greater than or equal to 7 days apart and greater than or equal to 1 prescription for disease-specific immunosuppressive drugs or steroids.

Researchers included 58,275 patients starting DPP4i combination therapy 1:1 matched to those starting non-DPP4i combination therapy.

Risks of rheumatoid arthritis and other autoimmune disease were significantly lower in the DPP4i group vs. non-DPP4i with the hazard ratio ( HR ) of 0.64 for rheumatoid arthritis, 0.53 for other autoimmune diseases, and 0.57 for composite autoimmune disease.

In sensitivity analysis, the risk of other autoimmune diseases and composite autoimmune disease was significantly reduced in initiators of DPP-4 inhibitors combination therapy compared to sulfonylurea combination therapy and thiazolidinediones combination therapy, but the risk of rheumatoid arthritis,was not.

In conclusion, in this large cohort of type 2 diabetes mellitus patients, initiating DPP4i combination therapy was associated with a decreased risk of incident rheumatoid arthritis or other autoimmune diseases compared to those initiating non-DPP4i combination therapy. These results suggest possible pharmacologic pathways for reducing the incidence of autoimmune diseases. ( Xagena )

Source: American College of Rheumatology ( ACR ) Annual Meeting, 2013