Effect of SGLT2 Inhibition on Body Water Distribution and Its Relevance to Body Composition Measures

Many studies have reported the effect of SGLT2 inhibition on body composition. However, its effect on water distribution and the resultant influence on body composition measures are still unclear. The subjects of this study consisted of 29 tofogliflozin (TOFO) -treated type 2 diabetic inpatients aged 48±14 years with BMI of 29.4±6.3 kg/m², and 29 age- and BMI-matched type 2 diabetic inpatients treated with other therapies. TOFO was administered for 7 days at a dose of 20 mg/day without changing the dose of other drugs. Average glucose levels assessed by CGM decreased from 188±43 to 142±32 mg/dL. Body composition and fluid status were estimated using a multifrequency BIA. The TOFO and the control groups lost 1.64±0.95 and 0.80±0.74 kg body weight, together with 1.31±1.02 and 0.38±0.87 kg body fat, respectively. The reduction of skeletal muscle was not statistically significant due to large variation in either group (0.21±0.84 and 0.39±1.03 kg, respectively). Thus we further analyzed factors associated with the skeletal muscle reduction. Although the change in skeletal muscle mass was correlated with changes in both body fat and body water, a multiple regression analysis showed that the change in intracellular water was the independent factor. Intracellular water was decreased in the TOFO group by 0.29±0.61 kg, but not in the control group. Extracellular water was not changed in either group. Serum sodium concentration was increased in the TOFO group (140.0±1.9 to 141.0±2.7 mEq/L) but not in the control group. The reduction in intracellular water was strongly correlated with that in skeletal muscle in the TOFO group (r=0.863), although there was an inverse correlation in the control group (r=-0.469). These observations indicate that SGLT2 inhibition results in the decrease of intracellular water likely due to increased osmotic diuresis despite plasma glucose reduction. The altered water distribution may affect the assessment of skeletal muscle by BIA.