Torcetrapib
CETP inhibition boosts the cholesterol-removing power of large HDL2b particles after a meal, but not their delivery to the liver (Atherosclerosis 2012)
Original title: Functionality of postprandial larger HDL2 particles is enhanced following CETP inhibition therapy
Researchers evaluated how CETP inhibition affects the ability of individual postprandial HDL subspecies to drive reverse cholesterol transport. Sixteen patients with low HDL cholesterol (below 40 mg/dl) were tested after a standardized mixed meal, both after 6 weeks of atorvastatin 10 mg per day alone and after adding torcetrapib 60 mg per day. The larger HDL2b and HDL2a subfractions showed greater capacity than smaller HDL3 particles to drive cellular free cholesterol efflux through both SR-BI and ABCG1 pathways, and CETP inhibition specifically enhanced HDL2b efflux capacity through both pathways, with only the SR-BI-dependent route further enhanced during the postprandial period. Postprandial lipemia independently reduced the capacity of total HDL particles to deliver cholesteryl esters to hepatic cells, regardless of treatment, while CETP inhibition improved HDL-cholesteryl ester delivery to the liver overall and maintained efficient cholesteryl ester return to the liver during the postprandial period.
Original abstract
Objective: To evaluate the impact of CETP inhibition on the capacity of individual postprandial HDL subspecies to promote key steps of the reverse cholesterol transport pathway.
Methods: The capacity of HDL particles to mediate cellular free cholesterol efflux and selective hepatic uptake of cholesteryl esters was evaluated throughout postprandial phase (0-8 h) following consumption of a standardised mixed meal before and after treatment for 6 weeks with atorvastatin alone (10 mg/d) and subsequently with combination torcetrapib/atorvastatin (60/10 mg/d) in 16 patients displaying low HDL-C levels (<40 mg/dl).
Results: The larger HDL2b and HDL2a subfraction displayed a superior capacity to mediate cellular free cholesterol efflux via both SR-BI and ABCG1-dependent pathways than smaller HDL3 subspecies. CETP inhibition specifically enhanced the capacity of HDL2b subfraction for both SR-BI and ABCG1 dependent efflux. However, only the SR-BI-dependent efflux to HDL2b subspecies can be further enhanced during postprandial lipemia following CETP inhibition. Concomitantly, postprandial lipemia was associated with a reduced capacity of total HDL particles to deliver cholesteryl esters to hepatic cells in a drug independent manner.
Conclusion: CETP inhibition specifically improves postprandial SR-BI and ABCG1-dependent efflux to larger HDL2b subspecies. In addition, CETP inhibition improves HDL-CE delivery to hepatic cells and maintains an efficient direct return of cholesteryl esters to the liver during postprandial lipemia.
HDL biologymechanismstorcetrapib
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.