Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Body Composition and Fluid Status in Cardiovascular Rehabilitation Patients with Coronary Artery Disease and Heart Failure.

: Sodium glucose cotransporter-2 (SGLT-2) inhibitors have emerged as integral therapeutic tools in the management of patients with cardiovascular-kidney-metabolic (CKM) syndrome. In addition to their well-documented effects on lowering glucose levels and cardiovascular- and reno-protective actions, SGLT-2 inhibitors, through a reduction in body weight (BW), generate changes in the body composition and volume status that have not been clearly studied. : This retrospective, observational longitudinal cohort, single-center study analyzed and compared body composition and fluid status measured by bioelectrical impedance analysis (BIA) from weeks 0 to 12 after the initiation of the cardiac rehabilitation (CR) program for coronary artery disease and heart failure in 59 patients who started treatment with SGLT-2 inhibitors (SGLT-2iG) and 112 patients without SGLT-2 inhibitors (non-SGLT-2iG). Changes between the baseline and week 12 in the SGLT-2iG and non-SGLT-2iG were -0.3 L ( = 0.003) and -0.03 L ( = 0.82) in extracellular water (ECW) ( = 0.05), -0.39 L ( < 0.001) and -0.14 L ( = 0.33) in intracellular water (ICW) ( = 0.12), -0.69 ( < 0.001) and -0.16 ( = 0.52) in total body water (TBW) ( = 0.08), and -0.01 ( = 0.37) and -0.001 ( = 0.25) in the ECW/TBW ratio, respectively. After 3 months of exercise therapy in the CR program, patients in the SGLT-2iG showed a greater decrease than the non-SGLT-2iG in weight (-1.34 kg, < 0.001 vs. -0.99, = 0.02), body mass index (BMI) (-0.45 kg/m, < 0.001 vs. -0.38, = 0.004), arm circumference (-0.57 cm, = 0.008 vs. -0.12 cm, = 0.21), waist circumference (-1.5 cm, = 0.04 vs. -0.11 cm, = 0.83), systolic blood pressure (SBP) (-8.9 mmHg, = 0.049 vs. -4.19, = 0.08), and diastolic blood pressure (DBP) (-5.15, = 0.03 vs. -2.85, = 0.01). The bioelectrical impedance analysis (BIA) revealed a significant decrease in body fat mass (BFM) and visceral fat area, without a loss of lean body mass (LBM) or skeletal muscle mass in the SGLT-2iG. : SGLT-2 inhibitors exert beneficial effects on body compartments and volume status. Although they induce modest weight loss, this appears to be mainly directed at ECW, BFM, and visceral fat, without a loss of LBM nor skeletal muscle mass, which could contribute to the observed CKM benefits.