Epigenetic changes of sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes mellitus

Objectives: The sodium-glucose co-transporter 2 (SGLT2) inhibitors have been found to possess cardioprotective and renoprotective effects in studies conducted recently. These beneficial effects may be due to the epigenetic modifications caused by the SGLT2 inhibitors. Metformin’s effects on DNA methylation have already been reported to produce both hypomethylation and hypermethylation. However, the effects of SGLT2 inhibitors on DNA methylation have not been thoroughly researched. Therefore, the purpose of the study was to ascertain whether type 2 diabetic patients taking SGLT2 inhibitors had changed DNA methylation. Materials and Methods: The patients on metformin and glimepiride treatment with poor glycaemic control were administered SGLT2 inhibitors as an add-on therapy. The blood samples for the determination of DNA methylation were collected before adding the SGLT2 inhibitors, and blood samples to determine DNA methylation were also recollected after 24 weeks of adding SGLT2 inhibitors. A total of 34 patients were analysed upon completion of the study. Results: DNA methylation of the patients receiving metformin and glimepiride treatment was increased from 3.09 as the baseline value to 4.24 when the patients were added with SGLT2 inhibitors as add-on therapy for 24 weeks. The glycaemic parameters, which include mean fasting plasma sugar (mg/dL), postprandial plasma sugar (mg/dL) and haemoglobin A1C (%), were changed from 172.47, 249.09 and 8.37 to 131.47, 191.71 and 7.35 ( P < 0.001), respectively. Conclusion: DNA methylation was significantly increased after adding 24 weeks of therapy with SGLT2 inhibitor medication to the patients already taking metformin and glimepiride for 24 weeks.