ILLUMINATE Sheds More Light

If one could design a metabolic intervention to prevent incident or recurrent cardiovascular events, it might look a lot like torcetrapib. Torcetrapib is the first cholesteryl ester transfer protein (CETP) inhibitor extensively studied in humans. Torcetrapib, in addition to statin therapy, raised high-density lipoprotein (HDL) by >70%, lowered low-density lipoprotein by 25%, and lowered triglycerides by ≈10%.1 This is an impressive profile for a pharmaceutical agent. What if someone told you that this therapy also improves glycemic control?Article see p 555That is precisely what Barter et al2 tell us in the current issue of Circulation . In a post hoc analysis of the Investigation of Lipid Level Management to Understand Its Impact in Atherosclerotic Events (ILLUMINATE) trial, the authors report the results of multiple glycemic measures among atorvastatin-treated patients randomly assigned to torcetrapib versus placebo. Torcetrapib/atorvastatin-treated patients had modest, but consistently lower, levels of plasma glucose and glycosylated hemoglobin than patients taking atorvastatin alone. These differences were observed in the setting of lower levels of plasma insulin, suggesting that torcetrapib was associated with better insulin sensitivity and less insulin resistance. These changes were more prominent in subjects with diabetes mellitus, but also seemed to be present in subjects without diabetes mellitus. These findings emerged early, within 1 month, and increased progressively during follow-up (12 months). The glycemic results in ILLUMINATE are subject to the same limitations as all post hoc analyses and could simply be the play of chance, 1 significant observation among many possible observations across multiple parameters tested. In addition, the relatively small effects on glycemic parameters could be seen as a variation across measurements. However the consistency of …