In clinical trials, a small increase in LDL cholesterol has been reported with sodium-glucose cotransporter 2 (SGLT2) inhibitors. The mechanisms by which the SGLT2 inhibitor empagliflozin increases LDL cholesterol levels were investigated in hamsters with diet-induced dyslipidemia. Compared with vehicle, empagliflozin 30 mg/kg/day for 2 weeks significantly… (More)
Figure 3—Proposed mechanisms for the alteration of cholesterol metabolism by empagliflozin. SGLT2 inhibition switches from carbohydrate to fat oxidation and stimulates ketone body production and hepatic cholesterol synthesis in fasting conditions. These metabolic alterations result in lower LDL receptor (LDL-r) expression and moderate increase in LDL-C levels. The reduced intestinal cholesterol absorption, which leads to higher macrophage- and LDL-derived cholesterol fecal excretion, remains to be further investigated. HMGCS1, HMG-CoA synthase 1; HMGCS2, HMG-CoA synthase 2; HMGCoA red, HMG-CoA reductase.