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.

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.

• Authors: Philip J Barter, Kerry-Anne Rye, Jean-Claude Tardif, David D Waters, S Matthijs Boekholdt, Andrei Breazna, John J P Kastelein
• Journal: Circulation (Circulation) Vol. 124 Issue 5 Pg. 555-62 (Aug 02 2011) ISSN: 1524-4539 [Electronic] United States
• PMID: 21804130 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticholesteremic Agents
• Blood Glucose
• Cholesterol, HDL
• Glycated Hemoglobin A
• Heptanoic Acids
• Hypoglycemic Agents
• Insulin
• Pyrroles
• Quinolines
• hemoglobin A1c protein, human
• torcetrapib
• Atorvastatin

Topics

• Aged
• Anticholesteremic Agents (therapeutic use)
• Atherosclerosis (complications, drug therapy)
• Atorvastatin
• Blood Glucose (drug effects)
• Cholesterol, HDL (blood)
• Diabetes Mellitus, Type 2 (complications, drug therapy)
• Dyslipidemias (complications, drug therapy)
• Female
• Glycated Hemoglobin (metabolism)
• Heptanoic Acids (therapeutic use)
• Homeostasis (drug effects)
• Humans
• Hyperglycemia (complications, drug therapy)
• Hypoglycemic Agents (therapeutic use)
• Insulin (blood)
• Insulin Resistance (physiology)
• Male
• Middle Aged
• Prospective Studies
• Pyrroles (therapeutic use)
• Quinolines (therapeutic use)