Effect of Empagliflozin on Erythropoietin Levels, Iron Stores, and Red Blood Cell Morphology in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease
Abstract
empagliflozin ◼ erythrocytes ◼ erythropoietin ◼ iron ◼ sodium-glucose transporter 2 inhibitors S odium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to improve cardiovascular outcomes, including hospitalization for heart failure and mortality, in people with and without diabetes mellitus. 1,2The mechanisms underlying this benefit remain unclear.Although several hypotheses have been suggested (including SGLT2 inhibitormediated diuresis and natriuresis, reduction in blood pressure and afterload, direct effects on myocardial sodium and calcium handling, alterations in myocardial energetics, reduction in left ventricular mass, and improved progenitor cell response), 3 a mediation analysis from the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) suggests that an increase in hematocrit may account for more than half of the mortality benefit observed.The consistent observation of an increase in hematocrit, even in those without diabetes mellitus, has led to the hypothesis that SGLT2 inhibitors may increase erythropoiesis via enhanced erythropoietin secretion by the kidney. 4This SGLT2 inhibitor-mediated increase in erythropoietin production (and resultant rise in hematocrit) could lead to systemic organ protection by virtue of its capacity as a circulating pleiotropic cytokine, known to favorably influence cardiomyocyte mitochondrial function, angiogenesis, cell proliferation, and inflammation.In addition,…
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