The extracellular volume status predicts body fluid response to SGLT2 inhibitor dapagliflozin in diabetic kidney disease

BACKGROUND: Sodium–glucose cotransporter 2 (SGLT2) inhibitors are an antihyperglycemic drug with diuretic action. We recently reported that the SGLT2 inhibitor dapagliflozin ameliorates extracellular volume expansion with a mild increase in urine volume. However, the impact of the pretreatment extracellular volume status on the body fluid response to SGLT2 inhibitors remains unclear. METHODS: Thirty-six diabetic kidney disease (DKD) patients were treated with dapagliflozin. The body fluid volume, including intracellular water (ICW), extracellular water (ECW) and total body water (TBW), were measured on baseline and day 7 using a bioimpedance analysis (BIA) device. The ECW/TBW and ECW were used as markers of the extracellular volume status. For a comparison, the extracellular volume status responses to loop diuretic furosemide (n = 16) and vasopressin V2 receptor antagonist tolvaptan (n = 13) were analyzed. RESULTS: The body weight, brain natriuretic peptide and body fluid parameters measured by a BIA (ICW, ECW, TBW, and ECW/TBW) were significantly decreased for 1 week after dapagliflozin administration. The change in the ECW/TBW in the high-ECW/TBW group (over the median value of 0.413) was significantly higher than in the low-ECW/TBW group (− 2.1 ± 0.4 vs. − 0.5 ± 0.4%, p = 0.006). Only with dapagliflozin treatment (not furosemide or tolvaptan treatment) was the baseline ECW/TBW significantly correlated with the changes in the ECW/TBW (r = − 0.590, p < 0.001) and ECW (r = − 0.374, p = 0.025). CONCLUSIONS: The pretreatment extracellular volume status predicts the body fluid response to the SGLT2 inhibitor dapagliflozin in DKD patients. The diminished extracellular fluid reduction effect of dapagliflozin in patients without severe extracellular fluid retention may contribute to maintaining a suitable body fluid status.