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

Anja Schork, Janine Saynisch, Andreas Vosseler, Benjamin Assad Jaghutriz, Nils Heyne, Andreas Peter, Hans-Ulrich Häring, Norbert Stefan, Andreas Fritsche, Ferruh Artunc, Anja Schork, Janine Saynisch, Andreas Vosseler, Benjamin Assad Jaghutriz, Nils Heyne, Andreas Peter, Hans-Ulrich Häring, Norbert Stefan, Andreas Fritsche, Ferruh Artunc

Abstract

Background: SGLT2-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.

Methods: In 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.

Results: At 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.

Conclusions: Body 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.

Keywords: Bioimpedance sprectroscopy; Body composition monitor; Diabetes mellitus; Fluid status; Overhydration; Renin–angiotensin–aldosterone system; SGLT2 inhibitor.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Course of body weight (a) and adipose tissue mass (ATM; b) under treatment with SGLT2 inhibitors. Left side shows absolute values, right side shows values normalized for baseline value. Whiskers indicate median and interquartile range. Friedman test was performed to test for significant differences during course of follow up; Wilcoxon Signed-Rank test was used to evaluate for differences between respective points of follow up; Bonferroni correction for multiple testing was performed
Fig. 2
Fig. 2
Course of overhydration (OH; a) and extracellular water (ECW; b) under treatment with SGLT2 inhibitors. Left side shows absolute values, right side shows values normalized for baseline value. Whiskers indicate median and interquartile range. Friedman test was performed to test for significant differences during course of follow up; Wilcoxon Signed-Rank test was used to evaluate for differences between respective points of follow up; Bonferroni correction for multiple testing was performed
Fig. 3
Fig. 3
Course of serum aldosterone concentration (a) and plasma renin activity (b) under treatment with SGLT2 inhibitors. Left side shows absolute values, right side shows values normalized for baseline value. Whiskers indicate median and interquartile range. Friedman test was performed to test for significant differences during course of follow up; Wilcoxon Signed-Rank test was used to evaluate for differences between respective points of follow up; Bonferroni correction for multiple testing was performed
Fig. 4
Fig. 4
Overhydration (OH; a), L/1.73 m2 and extracellular water (ECW; b), L/1.73 m2 in healthy controls, hypertensive patients with and without hydrochlorothiazide and in patients with type 2 diabetes with and without SGLT2 inhibitor. Values reported for patients with type 2 diabetes with SGLT2 inhibitor are values measured at the end of follow up period (day 180 of medication with SGLT2 inhibitor). Hypertensive patients with hydrochlorothiazide (HCT) have taken hydrochlorothiazide for at least 6 months. ANOVA analysis and t-tests performed for each pair reveal no difference in OH or ECW of patients with type 2 diabetes with SGLT2 inhibitors compared to healthy controls, patients with type 2 diabetes without SGLT2 inhibitor and hypertensive patients with and without hydrochlorothiazide. Whiskers indicate median and interquartile range

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