Dapagliflozin and other SGLT2 inhibitors are known to increase hematocrit. One possible mechanism is glycosuria and polyuria and the loss of fluid from the vascular compartment. However, since type 2 diabetes is a pro-inflammatory state and since hepcidin, a known suppressor of erythropoiesis, is increased in pro-inflammatory states, we investigated the possibility that dapagliflozin suppresses hepcidin concentrations and thus increases erythropoiesis. Twenty-two patients with type 2 diabetes and normal renal function (mean age: 62.1±1.7 years) were randomly treated with placebo or dapagliflozin 10 mg daily for 12 weeks. In the dapagliflozin group, there was a fall in HbA1c from 7.1±0.2% to 6.7±0.2% (p<0.05), increase in hemoglobin concentration from 13.2±0.8g/L to 13.8±0.4g/L (p<0.05) and in Hct from 40.2±1.3% to 41.9±1.8% (p<0.05). Plasma concentration of hepcidin fell from 265±26ng/mL to 215±24ng/mL (p<0.05). There was no significant change in any of these indices in the placebo group. Since one of the mechanisms through which hepcidin inhibits erythropoiesis is the suppression of the expression of ferroportin, which transports iron from iron storage cells into plasma, we also measured ferroportin expression in peripheral blood mononuclear cells. The expression of this transporter was not altered. We conclude that dapagliflozin suppresses hepcidin concentrations significantly, consistent with an increase in erythropoiesis and hematocrit but by a mechanism not involving ferroportin expression.


H. Ghanim: None. J.M. Hejna: None. S. Abuaysheh: None. T. Shah: None. J. Kumar: None. M. Batra: Speaker's Bureau; Self; Eli Lilly and Company. P. Dandona: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.