SGLT2 inhibitors: how do they affect the cardiac cells.

The first sodium-glucose cotransporter-2 inhibitor (SGLT2I), canagliflozin, was approved by the U.S. Food and Drug Administration for the treatment of type 2 diabetes in 2013. Since then, other members of this drug class (such as dapagliflozin, empagliflozin, and ertugliflozin) have become widely used. Unlike classical antidiabetic agents, these drugs do not interfere with insulin secretion or action, but instead promote renal glucose excretion. Since their approval, many preclinical and clinical studies have been conducted to investigate the diverse effects of SGLT2Is. While originally introduced as antidiabetic agents, the SGLT2Is are now recognized as pillars in the treatment of heart failure and chronic kidney disease, in patients with or without diabetes. The beneficial cardiac effects of this class have been attributed to several mechanisms. Among these, SGLT2Is inhibit fibrosis, hypertrophy, apoptosis, inflammation, and oxidative stress. They regulate mitochondrial function and ion transport, and stimulate autophagy through several underlying mechanisms. This review details the potential effects of SGLT2Is on cardiac cells.

Investigation of the Expression of CYP3A4 in Diabetic Rats in Xenobiotic Metabolism.

Objectives: This study investigated the impact of a high-fat diet streptozotocin (STZ)-induced diabetes and dapagliflozin treatment on hepatic protein expression of CYP3A4. Materials and Methods: In our study, 34 male Sprague-Dawley rats were randomly divided into four groups: Control, high-fat diet and STZ-induced diabetes, dapagliflozin-treated control, and dapagliflozin-treated diabetes. In the microsomes obtained from the livers of these rats, the protein expression levels of CYP3A4 were determined by Western blotting. Results: Hepatic CYP3A4 protein expression levels in the control group treated with dapagliflozin were significantly decreased compared with those in the control group. In addition, hepatic CYP3A4 protein expression levels were decreased in dapagliflozin-treated diabetic Sprague-Dawley rats compared with those in both control and diabetic group rats, but the difference between the groups was not statistically significant. Conclusion: According to these two results, the use of dapagliflozin inhibited hepatic CYP3A4 protein expression.