Empagliflozin (formerly known as
BI 10773) is a potent, competitive, and selective inhibitor of the
sodium glucose transporter SGLT2, which mediates
glucose reabsorption in the early proximal tubule and most of the
glucose reabsorption by the kidney, overall. Accordingly,
empagliflozin treatment increased urinary
glucose excretion. This has been observed across multiple species including humans and was reported under euglycemic conditions, in
obesity and, most importantly, in type 2 diabetic patients and multiple animal models of
type 2 diabetes and of
type 1 diabetes. This led to a reduction in
blood glucose, smaller
blood glucose excursions during oral
glucose tolerance tests, and, upon chronic treatment, a reduction in HbA1c in animal models and patients. In rodents, such effects were observed in early and late phases of experimental diabetes and were associated with preservation of pancreatic β-cell function. Combination studies in animals demonstrated that beneficial metabolic effects of
empagliflozin may also manifest when added to other types of anti-hyperglycemic treatments including
linagliptin and
pioglitazone. While some anti-hyperglycemic drugs lead to
weight gain,
empagliflozin treatment was associated with reduced
body weight in normoglycemic obese and non-obese animals despite an increased food intake, largely due to a loss of adipose tissue; on the other hand,
empagliflozin preserved
body weight in models of
type 1 diabetes.
Empagliflozin improved endothelial dysfunction in diabetic rats and arterial stiffness, reduced blood pressure in diabetic patients, and attenuated early signs of nephropathy in diabetic animal models. Taken together, the
SGLT2 inhibitor empagliflozin improves
glucose metabolism by enhancing urinary
glucose excretion; upon chronic administration, at least in animal models, the reductions in
blood glucose levels are associated with beneficial effects on cardiovascular and renal complications of diabetes.