Main effects caused by SGLT2 inhibitors in patients with type 2 diabetes and the mechanisms that determine them

• Vladimir V. Salukhov
• Kotova Margarita E.

Abstract

Today sodium-glucose cotransporter 2 inhibitors (SGLT2) are one of the most promising and modern classes of glucose-lowering drugs. Possessing a unique mechanism of action, at the kidney inducing chronic glycosuria level, SGLT2 inhibitors provide many clinical benefits, including a decrease in HbA_1c levels, body weight and blood pressure, and uric acid. But these drugs attracted special attention when they demonstrated a decrease in cardiovascular and renal events in patients with type 2 diabetes. Due to these effects not been associated with glycemic control, the expert community continues to determine the causes and mechanisms of such an effect on cardiovascular risk. This review assesses the main results of three clinical studies on the cardiovascular safety of empagliflozin, canagliflozin and dapagliflozin, respectively - EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI 58. The studies above, as well as experimental work, allowed us to expand our understanding of the key mechanisms of drugs in the SGLT2 inhibitors class. The main mechanisms should be recognized as glycosuria, natriuresis and osmotic diuresis, weight loss due to visceral fat, ketogenesis on the background of hyperglycemia a decrease in the level of intracellular calcium, modulation of sympathetic tone, which are discussed in detail in this review.

Keywords:type 2 diabetes, inhibitors of sodium glucose cotransporter type 2, cardiovascular safety, cardiovascular failure, EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI 58

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