Possible Mechanism of Hematocrit Elevation by Sodium Glucose Cotransporter 2 Inhibitors and Associated Beneficial Renal and Cardiovascular Effects
Abstract
his review focuses on the postulated mechanism underlying elevation of erythropoietin, hemoglobin, and hematocrit levels in patients with type 2 diabetes mellitus receiving sodium glucose cotransporter 2 (SGLT2) inhibitors and how this phenomenon is linked to reduced progression of chronic kidney disease, lower mortality, and a lower risk of heart failure hospitalization.SGLT2 inhibitor therapy is associated with a modest increase in hematocrit (2%-4%) relative to placebo, and this effect is consistent for all 4 SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin).In patients with type 2 diabetes mellitus and stage 2 or 3 chronic kidney disease, empagliflozin increases hematocrit regardless of renal function, whereas hematocrit is not increased by SGLT2 inhibitors in patients with type 2 diabetes mellitus and stage 4 chronic kidney disease.By their diuretic effects, SGLT2 inhibitors also increase urine volume, but this increase peaks at 24 hours after the start of SGLT2 inhibitor therapy, and urine volume returns to baseline within 1 week, whereas hematocrit continues to increase over 2 months.Thus, the time course of the change in urine volume after the initiation of SGLT2 inhibitor therapy is completely different from that of hematocrit, which means that the increase in hematocrit cannot be explained only by hemoconcentration resulting from diuresis.What other mechanisms could explain the elevation of hematocrit?The erythropoietin level…
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