Canagliflozin Improves Erythropoiesis in Diabetes Patients with Anemia of Chronic Kidney Disease

Background: We evaluated the erythropoietic effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, in type 2 diabetes patients with anemia of chronic kidney disease. Methods: Nine diabetes patients were enrolled and administered 100 mg canagliflozin once a day for 12 weeks. The patients received fixed doses of conventional antidiabetic drugs and renin-angiotensin system inhibitors for 8 weeks before enrollment; these drugs were continued during the study. Endpoints were changes in erythropoiesis parameters, including erythrocyte and reticulocyte count, hemoglobin, hematocrit, and serum erythropoietin (EPO) concentration from baseline to 12 weeks. All variables were measured every 2 weeks. Results: Serum EPO concentration increased by 38 [15-62]% (P = 0.043) between baseline and 2 and 4 weeks. Reticulocyte count transiently increased at 2 weeks. Erythropoiesis occurred after 2 weeks of canagliflozin treatment. Erythrocyte count (from 386 +/- 36 x 10(4)/mu L to 421 +/- 36 x 10(4)/mu L; P = 0.0009), hemoglobin (from 11.8 +/- 0.6 g/dL to 12.9 +/- 1.1 g/dL; P = 0.0049), and hematocrit (from 37.1 +/- 2.3% to 40.4 +/- 3.2%; P = 0.002) increased from baseline to study completion. Although there were no significant changes in transferrin saturation, serum ferritin levels were decreased (P = 0.003). Conclusions: Canagliflozin treatment led to an improvement in erythropoiesis in patients with impaired kidney function. The effect on erythropoiesis appeared to be due to an EPO production-mediated mechanism and might be independent of glycemic control; however, further studies are needed to clarify this since the present study had a small sample size and no comparator group.