Torcetrapib
Torcetrapib improved glycemic control in 6,661 diabetic ILLUMINATE participants despite the overall harm of the trial (Circulation 2011)
Original title: Effect of torcetrapib on glucose, insulin, and hemoglobin A1c in subjects in the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial
Because elevated HDL from genetic CETP deficiency is linked to lower plasma glucose, researchers conducted a post hoc analysis of the 6,661 diabetic patients in the ILLUMINATE trial to test the effect of torcetrapib on glycemic control. After 3 months, diabetic patients on torcetrapib plus atorvastatin had plasma glucose 0.34 mmol/L lower and insulin 11.7 uU/mL lower than those on atorvastatin alone (both P<0.0001), with homeostasis model assessment of insulin resistance decreasing from 49.1 to 47.3 in the torcetrapib arm versus an increase with atorvastatin alone (P<0.0001). At 6 months, hemoglobin A1c was 7.06% in the torcetrapib/atorvastatin arm versus 7.29% with atorvastatin alone (P<0.0001), and these glycemic benefits persisted through 12 months. Torcetrapib also lowered glucose and insulin in nondiabetic participants, though to a lesser degree. The authors conclude torcetrapib improved glycemic control in atorvastatin-treated type 2 diabetic patients, though whether this reflects its HDL-raising effect remains undetermined.
Original abstract
Background: High-density lipoproteins have antidiabetic properties in vitro. Furthermore, elevated high-density lipoprotein levels accompanying a genetic deficiency of cholesteryl ester transfer protein are associated with decreased levels of plasma glucose. We now investigate effects on glucose homeostasis of inhibiting cholesteryl ester transfer protein with torcetrapib.
Methods And Results: A post hoc analysis of the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial was conducted to investigate effects of the cholesteryl ester transfer protein inhibitor torcetrapib on glycemic control in the 6661 diabetic patients in the trial. At baseline, there were no differences between the 2 treatment arms with respect to plasma glucose, insulin, hemoglobin A(1c), or the homeostasis model assessment of insulin resistance. After 3 months, the diabetic subjects taking the combination of torcetrapib plus atorvastatin had plasma glucose levels 0.34 mmol/L lower (P<0.0001) and insulin levels 11.7 μU/mL lower (P<0.0001) than in those receiving atorvastatin alone. Homeostasis model assessment of insulin resistance values decreased from 49.1 to 47.3 (P<0.0001) in the torcetrapib/atorvastatin arm compared with an increase in homeostasis model assessment of insulin resistance in the atorvastatin arm. At the 6-month time point, the mean hemoglobin A(1c) level in the atorvastatin arm was 7.29% compared with 7.06% in the torcetrapib/atorvastatin arm (P<0.0001). These effects of torcetrapib remained apparent for up to 12 months. Torcetrapib also lowered both glucose and insulin levels in the participants without diabetes mellitus, although the effects were not as great as in those with diabetes mellitus.
Conclusions: Treatment with torcetrapib improves glycemic control in atorvastatin-treated patients with type 2 diabetes mellitus. It remains to be determined whether this effect is the consequence of raising high-density lipoprotein.at
Clinical Trial Registration: http:www.clinicaltrials.gov. Unique identifier: NCT00134264.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.