Dapagliflozin Suppresses Hepcidin And Increases Erythropoiesis

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Husam Ghanim 1, Sanaa Abuaysheh 1, Jeanne Hejna 1, Kelly Green 1, Manav Batra 1, Antione Makdissi 1, Ajay Chaudhuri 1, Paresh Dandona 1

Main idea: We conclude that dapagliflozin increases erythropoiesis and hematocrit through mechanisms that involve the suppression of hepcidin and the modulation of other iron regulatory proteins.

Abstract

Context: Dapagliflozin and other SGLT2 inhibitors are known to increase hematocrit, possibly due to its diuretic effects and hemoconcentration.

Objective: Since type 2 diabetes is a proinflammatory state and since hepcidin, a known suppressor of erythropoiesis, is increased in proinflammatory states, we investigated the possibility that dapagliflozin suppresses hepcidin concentrations and thus increases erythropoiesis.

Design: Prospective, randomized, and placebo-controlled study.

Setting: Single endocrinology center.

Patients: Fifty-two obese type 2 diabetes patients.

Intervention: Patients were randomized to either dapagliflozin (10 mg daily) or placebo for 12 weeks. Blood samples were collected before and after treatments and serum, plasma, and mononuclear cells (MNC) were prepared.

Main outcome measure: Hepcidin and other hematopoietic factors. Results: Following dapagliflozin treatment, there was a significant fall in HbA1c and a significant increase in hemoglobin concentration and hematocrit. Treatment significantly reduced circulating hepcidin and ferritin concentrations. There were no significant changes in any of these indices in the placebo group. The study was published in the Journal of Allergy and Clinical Pharmacology.

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