Abstract
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 6 months 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 6 months, HbA1c decreased by 0.8% (IQR 2.3; 0.4), body weight and BMI by 2.6 kg (1.5; 9.3) and 0.9 kg/m2 (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 − 0.5 L/1.73 m2 (− 0.1; − 0.9) and − 0.4 L/1.73 m2 (− 0.1; − 0.8) at day 3, respectively, and returned to the initial value after 3 and 6 months. Plasma renin activity increased by 2.1-fold (0.5; 3.6) at 1 month and returned to the initial level at month 3 and 6. Fluid status of patients with SGLT2 inhibitors after 6 months 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.
Highlights
sodium-coupled glucose transporter 2 (SGLT2)-inhibitors are potent antihyperglycemic drugs for patients with type 2 diabetes and have been shown to reduce body weight
We found that the reduction of body weight during treatment with the SGLT2 inhibitors empagliflozin and dapagliflozin is caused by changes in volume status with decrease of extracellular water during the first days of intake, and by decrease of adipose tissue mass during the following weeks and months
The diuretic effect of SGLT2 inhibitors seems to be most effective during the initial period of SGLT2 inhibition [38], and we showed that it causes changes in fluid status and could be responsible for fast acting beneficial effects on heart failure; reduction of adipose tissue that we confirmed in the follow up period of SGLT2 inhibition indicates that additional mechanisms for risk reduction in heart failure could gain importance in the long term course, such as lipid utilization [31], reduction of epicardial fat [32, 33], and effects on vascular endothelial function [50]
Summary
SGLT2-inhibitors are potent antihyperglycemic drugs for patients with type 2 diabetes and have been shown to reduce body weight. It is unclear which body compartments are reduced and to what extent. SGLT2-inhibitors increase urinary excretion of glucose by inhibiting its reabsorption via SGLT2 in the proximal tubule of the kidney, lowering blood glucose levels [1]. Besides their antidiabetic effect, loss of body weight has been observed consistently [2,3,4]. Changes of body composition during the first days after initiation of SGTL2 inhibitors have not been investigated yet
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