Dipeptidyl peptidase 4 inhibitor linagliptin can decrease the dosage of erythropoiesis-stimulating agents in patients on hemodialysis

Abstract

Background: Dipeptidyl peptidase 4 (DPP4) inhibitors are very useful for the treatment of type 2 diabetes, especially to patients undergoing hemodialysis (HD). The main action of DPP4 inhibitors is to increase the concentration of incretin which stimulate the insulin secretion from pancreatic beta cells. Recently, the extra-pancreatic actions of DPP4 inhibitors were suggested by many reports; a study has shown that hematopoiesis in mice after radiation or chemotherapy was enhanced receiving an oral DPP4 inhibitor sitagliptin. It suggests the possibility that DPP4 inhibitors can reduce the dosage of erythropoiesis-stimulating agents (ESAs) in HD patients. But there is no clinical report about the effect of DPP4 inhibitors on renal anemia in HD patients. This study was designed to confirm the clinical effect of DPP4 inhibitors on the reduction of dosage of ESA or improvement of renal anemia. Methods: Over a 6-month period from October 2013 to June 2014, a daily dose of DPP4 inhibitor linagliptin (5 mg/day) was administered orally to 25 patients on HD who were diagnosed with diabetes mellitus in our institution. The dosage of ESA darbepoetin alfa (DA), ESA-resistant index (ERI: DA dosage/hemoglobin), hemoglobin concentration, transferring saturation (TSAT), ferritin, and high-sensitivity C-reactive protein (hs-CRP) were measured and averaged for 3 months before and after the treatment. Results: At the end of the 6 months, 12 patients were excluded from the analysis due to death, hospitalization in another hospital, cancer, or withdrawal. After administration of linagliptin, the dosage of DA and ERI decreased significantly (P < 0.05, paired t test).The dosage of DA decreased from a mean ± SD of 23.9 ± 21.2 to 11.3 ± 9.7 (μg/week), and ERI decreased from 2.3 ± 2.1 to 1.0 ± 0.9. Hemoglobin concentration, white blood cell (WBC) count, platelet count, ferritin, and TSAT level were not different. Hs-CRP, as the marker of inflammation, was not different, too. Conclusions: This study suggests that DPP4 inhibitor linagliptin can decrease the dosage of ESA without the influence of iron metabolism and inflammation. The previous study has shown that DPP4 cleaves within N-terminal of erythropoietin and decreases their activity in mice. We speculate that DPP4 inhibitors can increase the concentration of erythropoietin by inhibiting this action of DPP4.