Effects of empagliflozin and dapagliflozin, SGLT2 inhibitors, on miRNA expressions in diabetes-related cardiovascular damage in rats

Type 2 diabetes mellitus (T2DM) has become a global health concern due to its rapidly increasing prevalence and associated complications. Empagliflozin and dapagliflozin, sodium-glucose co-transporter 2 (SGLT2) inhibitors, have widely used in the management of T2DM. Moreover, empagliflozin and dapagliflozin reduce the risk of cardiovascular events and associated mortality both with and also without diabetes. In the present study, it was investigated empagliflozin and dapagliflozin effects on miRNA expression in nicotinamide/streptozotocininduced T2DM rats. The male/female rats were divided into four groups: Control, T2DM, T2DM + Empagliflozin, and T2DM + Dapagliflozin. The body weights were monitored weekly and blood pressure measurement were evaluated first and last week. IL-1 beta, SOD, RAGE, and cTnI levels in serum and heart tissue were detected by ELISA. The RT-PCR was used to analyze the expression levels of miRNAs in the heart tissue of diabetic rats. As a result, the most remarkable findings miR-223, miR-373, miR-22, miR-9, miR-146a, miR-21, miR-144, miR-221, and miR-34a had significantly higher expressions in the control group. Moreover, miR-146a and miR-34a levels are remarkably increased empagliflozin group comparison to the T2DM group. The miR-146a expression was increased dapagliflozin group comparison to the T2DM group. Additionally, treatments with empagliflozin and dapagliflozin showed improvements in histopathological and biochemical examinations.