Sodium-Glucose Transporter Inhibitors and Diabetic Nephropathy in Humans and Animal Model

Abstract

Diabetic nephropathy as the leading cause for end stage renal disease and replacement therapy is increasing every year. Treatment of T2DM with the present oral blood glucose lowering drugs and insulin is challenging, with an enormous number of patients are able to achieve the target glycaemic control (HbA1C<6.5%). Despite the use of new Insulin compounds and different recommended combination of oral anti-diabetic drugs, the benefits of these recommendations are offset by side effects such as weight gain and recurrent hypoglycaemia. Therefore, the need for new agents that control blood glucose strictly and have other proactive cellular pathways is challenging. The sodium glucose transporter protein 2 (SGLT2) inhibitors, are recently being widely used. The main therapeutic effect of these new drugs, SGLT2 inhibitors (SGLT2-I), is lowering the blood glucose levels via inhibitory effect on the transport of glucose and sodium in the proximal tubular cells by sodium glucose transport 1. SGLT2-I reduce plasma sodium level by natriuretic and diuresis, with decreasing blood pressure and body weight. These new medications can be used as first and second lines of treatment especially in patients with normal glomerular filtration rate, with or without cardiovascular complications. The most effective combination of SGLT2I is Metformin especially in albuminuria and slowing the progression of diabetic nephropathy especially if initiated in early stages of DM. The new class of medication (SGLT2I) are less effective in patients with moderate CKD (eGFR<45 ml/min). This review will focus on the new pathways such autophagy as a new pathway where SGLT2 are involved with protective effects.