Research Projects

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are oral anti-diabetic drugs approved for use in patients with type 2 diabetes mellitus (T2D). These drugs inhibit SGLT2 in the proximal renal tubules, reducing renal tubular glucose reabsorption and lowering blood glucose levels independently of insulin action. They have shown beneficial pleiotropic effects, including cardioprotection, renoprotection, weight loss, blood pressure reduction, and improvement in non-alcoholic fatty liver disease. SGLT2i has also been shown to improve endothelial dysfunction, although most data is based on animal or in vitro studies. Studies in human subjects are limited, with flow-mediated dilation (FMD) being used as a surrogate to assess endothelial function. Endothelial dysfunction is the cornerstone of all microvascular complications in diabetes, and epigenetic alterations are responsible for this dysfunction. The renoprotective effects of SLGT2i could reflect an overall improvement in endothelial dysfunction, which could result from underlying and yet unrecognized epigenetic alterations mediated by this class of drug. A randomized placebo-controlled blinded endpoint trial is proposed to study the effect of dapagliflozin on specific microRNAs levels in T2D patients with albuminuria, suggesting diabetic nephropathy. The study will recruit 80 SGLT2i-naïve T2D men with albuminuria and randomly assign them into two groups: Group A to receive dapagliflozin 10 mg+ standard of care and Group B to receive placebo+standard of care.