The impact of Dapagliflozin, and Empagliflozin on Na+/Li+ countertransport in erythrocyte membranes of healthy volunteers in acute drug tests
Authors: Khasanov N , Kapralova L , Khastieva D , Melnichuk M , Samsonova D , Shamsutdinova D 
Published: November 2020

Abstract

Background
The formation of the effect of SGLT 2 inhibitors on the cardiovascular system implies inhibition of the Na+/H+exchanger (NHE) that leads to a decrease in the concentration of Na+, which in turn contributes to a decrease in the concentration of Ca2+ in the cardiomyocyte (S. Verma, J. McMurray, 2018). However, this effect may be different against the background of exposure to empagliflozin and dapagliflozin. A study of A. Baartscheer (2017) demonstrated the reduction of [Na+], systolic and diastolic [Ca+] in cardiomyocyte is affected by Empagliflozin. N.N. Hamouda's research shows that Dapagliflozin reduce [Na+], systolic, but not diastolic [Ca2+] in cardiomyocytes. In this regard, studying the Na+/Na+ exchanger (which is the mode of the NHE operation) activity estimated by the Na+/Li+countertransport (SLC) in the erythrocyte membrane (K. Morgan, M. Canessa, 1990; M. Canessa, 1989) is of great interest.

Purpose
A study of the impact of Dapagliflozin, and Empagliflozin on SLC in erythrocyte membranes of healthy volunteers in acute drug tests.

Materials and methods
10 healthy volunteers (7 men and 3 women) were included in the study. The mean age of the study group was 24±0,6 years. The volunteers took singly Dapagliflozin, and Empagliflozin separately in one-month intervals. The activity of SLC was determined before drug consumption, as well as 2, 12, and 24 hours after consumption by the method of M.Canessa (1980). All data were tested for normality using the Kolmogorov–Smirnov test and statistically tested by paired Student t-test.

Results
Mean speeds of SLC before the drugs were administered was 289.1±33.1 mmol/L cell*h in the Dapagliflozin group and 287.8±37.3 mmol/L cell*h in the Empagliflozin group (p=0.979). Two hours after Dapagliflozin was administered, the speed of SLC increased to 76.3±17.0 mmol/L cell*h (95% CI: 37.9–114.7) and was maximum 365±41.6 mmol/L cell*h (p=0.002) for observation period. Then after 12 and 24 hours decreasing SLC activity was observed. However, the values were higher than the initial level and amounted to 335.5±39.18 mmol/L cell*h (p=0.024) after 12 hours and 331±31.8 mmol/L cell*h (p=0.001) after 24 hours. Two hours after Empagliflozin was administered, the speed of SLC not significantly changed and amounted to 287.8±37.3mmol/L cell*h (p=0.7). After 12 hours, the speed not significantly increased to 23.4±11.9 (95% CI: 4.6–51.4) mmol/L cell*h and amounted to 311.1±39.2 (p=0.08), with the subsequent decrease of speed within 24 hours to 277.6±40.5 mmol/L cell*h (p=0.5). Thus Dapagliflozin and Empagliflozin have different effects on the function of Na+/Na+ exchanger which may differently affect the changing of the [Na+] and [Ca2+] in the cardiomyocyte.

Conclusions
1. When Dapagliflozin was administered the SLC speed reached its maximum level after 2h and maintained higher than initial level after 12h and 24h.
2. When Empagliflozin was administered no significant change in SLC speed was observed.

Funding Acknowledgement
Type of funding source: None