Effect of empagliflozin on adenosine triphosphate levels in vivo in patients with type 2 diabetes mellitus combined with heart failure
U Omurzakova, M Breidert, M Moldobaeva, N Toktogulova, P EftekhariAbstract
Background
Heart failure (HF) is a common and clinically significant complication in patients with type 2 diabetes mellitus (DM) . Sodium-glucose cotransporter-2 inhibitors reduce mortality in patients with type 2 DM and HF. Its cardioprotective effect is possible due to an increase in adenosine triphosphate (ATP) levels, which indicates metabolically active cells.
Purpose
To evaluate the effect of empagliflozin on adenosine triphosphate level in patients with type 2 DM combined with HF in vivo.
Materials and methods
The prospective study included 45 patients (men n=34, women n=11) with previously diagnosed type 2 DM combined with HF (age 45-75 years) who had not previously taken empagliflozin. The mean age of patients was 63.9±7.2 years, body mass index (BMI) - 29.4±4.5kg/m2, glycated hemoglobin (HbA1c) 8,8±1.8%, left ventricular ejection fraction - 39,6±8,1%, B-type natriuretic peptide (BNP) - 310,0±486,2 pg/ml. Ex vivo analysis was performed to assess the impact of empagliflozin on cellular ATP levels at the doses of 0.1µM, 1µM, and 10µM (in vitro) by Cell Titer- Glo Luminescent Cell Viability Assay. Out of 45 patients, 20 were treated with empagliflozin (in vivo), starting at doses ranging from 10 to 25mg once a day for 12 weeks in addition to their standard therapy. After 12 weeks, blood samples were collected from these patients for ex vivo analysis to assess ATP levels. Informed written consent was obtained from each participant before the start of the study. Statistical processing was performed using the SPSS program (version 23.0). The Wilcoxon T-test and Mann-Whitney U-test were used to analyze quantitative indicators; statistically significant differences were considered at p < 0.05.
Results
Ex vivo analysis of blood samples collected at baseline (week 0) and treated with empagliflozin at concentrations of 0.1 µM, 1 µM, and 10 µM demonstrated no significant alterations in ATP levels. In the second phase of the study, following 12 weeks of in vivo empagliflozin treatment, ATP activity increased significantly (p=0.001) from baseline (Table 1). The study cohort exhibited a trend toward a reduction in BMI (from 29.12 ± 4.82 kg/m² to 28.40 ± 4.22 kg/m², p = 0.05). The HbA1c levels decreased from 9.02 ± 1.42% to 8.83 ± 1.11%, reflecting improved glycemic control following treatment. BNP concentrations declined from 231.03 ± 378.51 pg/ml to 208.39 251.22 pg/ml, potentially indicating a beneficial effect of therapy on myocardial function. The left ventricular ejection fraction remained relatively stable, with no significant change (p > 0.05).
Conclusion
Our study demonstrates that empagliflozin increases cellular ATP levels in vivo in patients with type 2 DM and concomitant HF, potentially contributing to its cardioprotective effects and therapeutic efficacy. These findings may have implications for optimizing therapeutic management in patients receiving empagliflozin and could serve as a biomarker for treatment adherence monitoring.Raw ATP level before and after treatment