The Elevation of Hematocrit after Administration of SGLT2 Inhibitors Does Not Correlate with Plasma Osmolarity in Japanese Subjects with Type 2 Diabetes

It has been reported that hematocrit is elevated after administration of sodium-glucose cotransporter 2 (SGLT2) inhibitors. However, it remains controversial whether this elevation is caused by its diuretic effect. In this study, we aimed to clarify the mechanism of hematocrit elevation by examining the correlation between hematocrit and several parameters reflecting diuretic effects in subjects with type 2 diabetes who were treated with SGLT2 inhibitors. A total of 70 subjects (male: n=45, age: 53.5±10.1 SD years, BMI: 29.3±4.5 kg/m², HbA1c: 8.8±1.2%) with type 2 diabetes who were newly administered SGLT2 inhibitors from June 2014 to March 2017 were retrospectively identified from our database. Changes in HbA1c, hematocrit, urine specific gravity, uric acid, serum creatinine and plasma osmolarity levels between before and 30, 60, 90 and 120 days after the administration of the drugs were evaluated. Plasma osmolarity was calculated by the formula (2 x (Na[mEq/l] + K[mEq/l])) + (BUN[mg/dl] / 2.8) + (glucose[mg/dl] / 18). HbA1c was significantly decreased (30d: -0.57±0.53%; p=0.0vs. basal value, 60d: -0.88±1.04; p=0.002, 90d: -0.65±1.10; p<0.001, 120d: -0.79±1.22; p<0.001). Hematocrit was increased immediately after and remained high over 120 days (1.3±2.1%; p=0.05, 1.5±3.0; p=0.44, 2.5±2.8; p=0.002, 2.1±2.6; p=0.005). Urine specific gravity was also increased (0.007±0.01g/ml; p<0.001, 0.003±0.010; p=0.02, 0.004±0.009; p=0.03, 0.007±0.011; p<0.001). However, uric acid (30d: -0.10±0.80mg/dl; p=0.70), serum creatinine (0.04±0.07mg/dl; p=0.32) and plasma osmolarity (0.87±4.34mOsm/l; p=0.31) did not show change. No correlations were observed between changes in hematocrit and serum creatinine, uric acid or plasma osmolarity.

In conclusion, our data indicate that the elevation of hematocrit after the administration of SGLT2 inhibitors is unlikely to be caused by hemo-concentration via diuretic effect.