Torcetrapib
Torcetrapib cuts apoB-48 production by nearly half, but the effect vanishes in patients already on atorvastatin (J Lipid Res 2012)
Original title: Effects of CETP inhibition on triglyceride-rich lipoprotein composition and apoB-48 metabolism
This study examined how CETP inhibition with torcetrapib affects triglyceride-rich lipoprotein (TRL) composition and apoB-48 metabolism in subjects with low HDL cholesterol, either untreated (n=9) or on atorvastatin 20 mg daily (n=9). After 4 weeks of placebo followed by 4 weeks of torcetrapib 120 mg once daily, and in a subset given 120 mg twice daily for an additional 4 weeks, isotope tracer kinetics of TRL apoB-48 were measured. Relative to placebo, torcetrapib markedly reduced TRL cholesteryl ester levels in all groups (at least -69%, p < 0.005). ApoB-48 pool size and production rate fell in the non-atorvastatin once-daily group (pool size -49%, production -49%, both p < 0.01) and twice-daily group (pool size -30%, production -27%), but in the atorvastatin cohort, where apoB-48 was already lowered by the statin, torcetrapib produced no further change, indicating CETP inhibition reduces apoB-48 concentrations by cutting its production, an effect not seen on top of atorvastatin.
Original abstract
Cholesteryl ester transfer protein (CETP) facilitates the transfer of HDL cholesteryl ester to triglyceride-rich lipoproteins (TRL). This study aimed to determine the effects of CETP inhibition with torcetrapib on TRL composition and apoB-48 metabolism. Study subjects with low HDL cholesterol (<40 mg/dl), either untreated (n = 9) or receiving atorvastatin 20 mg daily (n = 9), received placebo for 4 weeks, followed by torcetrapib 120 mg once daily for the next 4 weeks. A subset of the subjects not treated with atorvastatin participated in a third phase (n = 6), in which they received torcetrapib 120 mg twice daily for an additional 4 weeks. At the end of each phase, all subjects received a primed-constant infusion of [5,5,5-(2)H(3)]L-leucine, while in the constantly fed state, to determine the kinetics of TRL apoB-48 and TRL composition. Relative to placebo, torcetrapib markedly reduced TRL CE levels in all groups (≥-69%; P < 0.005). ApoB-48 pool size (PS) and production rate (PR) decreased in the nonatorvastatin once daily (PS: -49%, P = 0.007; PR: -49%, P = 0.005) and twice daily (PS: -30%, P = 0.01; PR: -27%, P = 0.13) cohorts. In the atorvastatin cohort, apoB-48 PS and PR, which were already lowered by atorvastatin, did not change with torcetrapib. Our findings indicate that CETP inhibition reduced plasma apoB-48 concentrations by reducing apoB-48 production but did not have this effect in subjects already treated with atorvastatin.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.