Abstract
Sodium glucose co-transporter 2 (SGLT2) inhibitors are effective antihyperglycemic agents by inhibiting glucose reabsorption in the proximal tubule of the kidney. Besides improving glycemic control in patients with type 2 diabetes, they also have additional favorable effects, such as lowering body weight and body fat. Several clinical studies have demonstrated their positive effect in reducing cardiovascular morbidity and mortality. Furthermore, the use of SGLT2 inhibitors were associated with fewer adverse renal outcomes comparing to other diabetic agents, substantiating their renoprotective effect in diabetic patients. SGLT2 inhibitors have also remarkable effect on lipid metabolism acting at different cellular levels. By decreasing the lipid accumulation, visceral and subcutaneous fat, they do not only decrease the body weight but also change body composition. They also regulate key molecules in lipid synthesis and transportation, and they affect the oxidation of fatty acids. Notably, they shift substrate utilization from carbohydrates to lipids and ketone bodies. In this review we intended to summarize the role of SGLT2 inhibitors in lipid metabolism especially on lipoprotein levels, lipid regulation, fat storage and substrate utilization.
Highlights
There are six identified SGLT proteins in humans, of which the SGLT1 and Sodium glucose co-transporter 2 (SGLT2) receptors have been studied more thoroughly in recent years
While SGLT1 is primarily expressed in the intestines, SGLT2 is most abundant in the renal cortex, where it plays an essential role in renal glucose reabsorption
Several studies have proved that SGLT2 inhibitors are associated with reduced cardiovascular morbidity and mortality, including heart failure, and vascular diseases [2,3,4,5,6]
Summary
There are six identified SGLT (sodium glucose co-transporter) proteins in humans, of which the SGLT1 and SGLT2 receptors have been studied more thoroughly in recent years. The contradiction may be resolved by the results provided by Hayashi et al showing that dapagliflozin decreased sd LDL, and increased lb LDL levels after 12 weeks of dapagliflozin therapy (5 mg/die) in type 2 diabetic patients [15] This effect on LDL subclasses ratio may play a significant role in SGLT2 inhibitors’ cardioprotective property [32,33], provided it is a class effect. Concerning HDL level, according to Kamijo et al after 12 weeks of canagliflozin administration (100 mg/die) the very large high-density lipoprotein (VLHDL) and large high-density lipoprotein (LHDL) values showed a significant increase, of 10.9% and 11.5% respectively These beneficial changes might contribute to subsequent reduction of cardiovascular outcomes, caused by SGLT2 inhibitors [34]
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