Epigenetic effect of SGLT-2 inhibitor drugs in diabetic patients with low ejection fraction heart failure (lvef<40%)

Heart failure continues to be one of the most important causes of mortality and morbidity worldwide. The mechanism of action of SGLT-2 inhibitor drugs, which have recently been included in the list of drugs that should be used in the guidelines due to their direct effect on mortality in the treatment of heart failure, is still not fully known. In this study, we investigated the possible epigenetic effect of this group of drugs by looking for changes in the levels of some microRNAs in heart failure patients with SGLT-2 use. Forty patients with an ejection fraction of less than 40% in the cardiology clinic of our university and deemed suitable for SGLT-2 inhibitor use by endocrinology and 20 healthy volunteers were included in the study. The levels of miRNA-21, miRNA-132, miRNA-499 and miRNA-210 were analysed by Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) in blood samples obtained from healthy volunteers before and 3 months after drug use. There was a statistically significant increase in Mir-21 and Mir-499 gene expression levels in the third month after drug use (p=0.005). Although there was a statistically significant increase in Mir-210 expression level in patients, there was no change after drug use. In terms of Mir-132 expression level, there was no statistically significant difference between the groups (p = 0.421). In conclusion, one of the mechanisms of action of SGLT-2 inhibitor drugs may be by epigentically changing miRNA levels (miR-21, miR-499).