Effect of SGLT2 inhibitors on body composition, fluid status and renin-angiotensin-aldosterone system in type 2 diabetes: a prospective study using bioimpedance spectroscopy

BackgroundSGLT2-inhibitors are potent antihyperglycemic drugs for patients with type 2 diabetes and have been shown to reduce body weight. However, it is unclear which body compartments are reduced and to what extent.MethodsIn this longitudinal observational study, we analyzed the body composition of 27 outpatients with type 2 diabetes mellitus during the first week and up to 6months after initiation of treatment with SGLT2-inhibitors (n=18 empagliflozin, n=9 dapagliflozin) using bioimpedance spectroscopy (BCM, Fresenius). Fluid status of hypertensive patients taking medication with hydrochlorothiazide (n=14) and healthy persons (n=16) were analyzed for comparison.ResultsAt 6months, HbA1c decreased by 0.8% (IQR 2.3; 0.4), body weight and BMI by 2.6kg (1.5; 9.3) and 0.9kg/m(2) (0.4; 3.3), respectively. Bioimpedance spectroscopy revealed significant decrease in adipose tissue mass and fat tissue index while lean tissue parameters remained stable. Overhydration (OH) and extracellular water (ECW) decreased by -0.5L/1.73m(2) (-0.1; -0.9) and -0.4 L/1.73m(2) (-0.1; -0.8) at day 3, respectively, and returned to the initial value after 3 and 6months. Plasma renin activity increased by 2.1-fold (0.5; 3.6) at 1month and returned to the initial level at month 3 and 6. Fluid status of patients with SGLT2 inhibitors after 6months showed no difference from that of hypertensive patients taking hydrochlorothiazide or healthy persons.ConclusionsBody weight reduction under the treatment with SGLT2-inhibitors is caused by reduction of adipose tissue mass and transient loss of extracellular fluid, which is accompanied by upregulation of renin-angiotensin-aldosterone system (RAAS). Permanent loss of extracellular water does not occur under SGLT2 inhibition.