Beneficial effects of sodium-glucose cotransporter 2 inhibitors for preservation of pancreatic β-cell function and reduction of insulin resistance.

Type 2 diabetes mellitus is characterized by insulin resistance in various insulin target tissues, such as the liver, adipose tissue, and skeletal muscle, and insufficient insulin secretion from pancreatic β-cells. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, which are newly developed antidiabetic agents, decrease blood glucose levels by enhancing urinary glucose excretion and thereby function in an insulin-independent manner. Sodium-glucose cotransporter 2 inhibitors exert beneficial effects to reduce insulin resistance and preserve pancreatic β-cell function. In addition, SGLT2 inhibitors exhibit a variety of beneficial effects in various insulin target tissues, such as amelioration of fatty liver, reduction of visceral fat mass, and increasing glucose uptake in skeletal muscle. Furthermore, SGLT2 inhibitors protect pancreatic β-cells against glucose toxicity and preserve insulin secretory capacity. Together, these observations indicate that SGLT2 inhibitors are promising newly developed antidiabetic agents that are gaining attention in both clinical medicine and basic research.