HDL biology
Ezetimibe lowers CETP mass by 20 percent in most type 2 diabetes patients, tracking with HDL subclass shifts (Endocr J 2012)
Original title: Ezetimibe, an inhibitor of Niemann-Pick C1-like 1 protein, decreases cholesteryl ester transfer protein in type 2 diabetes mellitus
Treating 23 hypercholesterolemic patients with type 2 diabetes with ezetimibe 10 mg daily for 12 weeks, researchers measured HDL subclasses, CETP mass, and LCAT activity. HDL-C rose 5% (P less than 0.05) and HDL2-C rose 12% (P less than 0.01). Twenty-one of the 23 patients had decreased CETP mass, averaging a 20% reduction (P less than 0.0001), while LCAT activity fell 6% (P less than 0.01). Changes in HDL2-C correlated positively with changes in CETP mass, while HDL3-C changes correlated inversely with CETP mass, and the change in HDL-C correlated positively with the change in LCAT activity, suggesting ezetimibe's effects on HDL metabolism and reverse cholesterol transport, particularly through CETP, may contribute to its antiatherosclerotic action.
Original abstract
To address the effects of ezetimibe on high-density lipoprotein (HDL) metabolism, the HDL subclasses, cholesteryl ester transfer protein (CETP), and lecithin-cholesterol acyltransferase (LCAT) were measured in patients with type 2 diabetes mellitus (T2DM). Twenty-three hypercholesterolemic patients with T2DM were treated with 10 mg of ezetimibe daily for 12 weeks. Plasma total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol (C), HDL-C, HDL(2)-C, HDL(3)-C, CETP mass, and LCAT activity were measured. HDL-C and HDL(2)-C increased by 5% (p<0.05) and 12% (p<0.01), respectively, in response to ezetimibe. Of the 23 patients, 21 had decreased CETP mass, which led to an average reduction of 20% (p<0.0001). LCAT activity also decreased by 6% (p<0.01). A significant positive correlation was found in the changes from baseline between HDL(2)-C and CETP mass, whereas a significant inverse relationship was observed between HDL(3)-C and CETP mass. Furthermore, the change in HDL-C was positively correlated with the change in LCAT activity. In conclusion, ezetimibe may affect HDL metabolism and reverse cholesterol transport, especially CETP, in T2DM. These observations may provide some insights into how ezetimibe prevents atherosclerosis.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.