Enhancement of the serum chloride concentration by administration of sodium-glucose cotransporter-2 inhibitor and its mechanisms and clinical significance in type 2 diabetic patients: a pilot study

Chloride is a key electrolyte that regulates the body fluid distribution. Accordingly, manipulating chloride kinetics by selecting a suitable diuretic could be an attractive strategy for correcting body fluid dysregulation. Therefore, this study examined the effects and contributing factors of a sodium-glucose cotransporter-2 inhibitor (SGLT2i) on the serum chloride concentration in type 2 diabetic (T2DM) patients without heart failure (HF). This study was a retrospective single-center observational study that enrolled 10 T2DM/non-HF outpatients for whom the SGLT2i empagliflozin (daily oral dose of 10 mg) was prescribed. Among these 10 patients, 6 underwent detailed clinical testing that included hormonal and metabolic blood tests. Empagliflozin treatment for 1-2 months decreased body weight (- 2.69 ± 1.9 kg; p = 0.002) and HbA1c (- 0.88 ± 0.55%; p = 0.0007). The hemoglobin (+ 0.27 ± 0.36 g/dL; p = 0.04) and hematocrit (+ 1.34 ± 1.38%; p = 0.014) values increased, but the serum creatinine concentration remained unchanged. The serum chloride concentration increased from 104 ± 3.23 to 106 ± 2.80 mEq/L (p = 0.004), but the sodium and potassium concentrations did not change. The spot urinary sodium concentration decreased from 159 ± 43 to 98 ± 35 mEq/L (p