Abstract
BackgroundSodium–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.MethodsThirty-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.ResultsThe 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).ConclusionsThe 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.
Highlights
Sodium–glucose cotransporter 2 (SGLT2) inhibitors are an antihyperglycemic drug with diuretic action
We recently reported that the SGLT2 inhibitor dapagliflozin predominantly decreased the extracellular volume with a mild increase in the urine volume in diabetic kidney disease (DKD) patients with fluid retention [7, 8]
Extracellular volume expansion, which is represented as an increased over-hydration index or the ratio of extracellular water (ECW) to total body water (TBW) (ECW/TBW), as measured by bioimpedance analysis (BIA) device, predicts high mortality and adverse cardio-renal outcomes in patients with chronic kidney disease (CKD) [9,10,11,12]
Summary
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. Sodium–glucose cotransporter 2 (SGLT2) inhibitors are anti-diabetic drugs that increase the urinary glucose excretion by inhibiting SGLT2 in the early proximal tubule [1, 2]. Recent clinical trials have shown that SGLT2 inhibitors exhibit cardio-renal protective properties in patients with diabetes mellitus and diabetic kidney disease (DKD) [3, 4]. We recently reported that the SGLT2 inhibitor dapagliflozin predominantly decreased the extracellular volume with a mild increase in the urine volume in DKD patients with fluid retention [7, 8]. The reduction in the extracellular volume expansion through SGLT2 inhibition may be a promising cardio-renal protective mechanism in these patients
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