An analysis of the ILLUMINATE trial data revealed new
findings: Torcetrapib, a cholesteryl ester transfer protein inhibitor, may
improve HDL levels and blood glucose in those with diabetes who are also taking
Researchers discovered the beneficial effects of
torcetrapib while analyzing data from the Investigation of Lipid Level
Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE)
trial, which was halted in 2006 because patients with diabetes assigned to
torcetrapib and atorvastatin (Lipitor, Pfizer) had more cardiovascular problems
and a higher mortality rate vs. patients assigned to atorvastatin and a
placebo. Researchers later determined that the adverse events were related to
other effects of torcetrapib, not its cholesteryl ester transfer protein (CETP)
inhibition, according to a press release from the American Heart Association.
Data from ILLUMINATE showed that after 3 months of
treatment, more than 6,600 patients with diabetes who were taking torcetrapib
and atorvastatin had lower fasting blood glucose levels (0.34 mmol/L) and
fasting insulin levels (11.7 mcU/mL) than patients taking statin and placebo.
Insulin resistance also improved in the investigational combination therapy
group. After 6 months, average blood glucose levels were lower in the
torcetrapib and atorvastatin group (7.06%) compared with the statin and placebo
group (7.29%). Additionally, HDL levels improved 66.8% after 1 year with
torcetrapib and atorvastatin compared with a minimal change with statin and
placebo. Researchers said it is unclear whether torcetrapibs effect on
HDL may account, in part, for the improvement in diabetes control. Torcetrapib
also improved glucose and insulin measurements in study participants without
diabetes, although not as much.
The possibility that CETP inhibitor drugs may not
only reduce the risk of [myocardial infarction] and stroke, but may also
improve the control of blood sugar in people with diabetes, is an exciting
prospect that may translate into real health benefits for people with
diabetes, Philip Barter, MBBS, PhD, director of the Heart Research
Institute at University of Sydney, Australia, said in a press release.
Although torcetrapibs effect on diabetes was not
as effective as other commonly used antidiabetic therapies, inhibition of
CETP has the potential to prevent a worsening of diabetic control that often
occurs in people taking statin drugs, Barter said.
ILLUMINATE included more than 15,000 participants aged
45 to 75 years with a history of MI, stroke, chest pain, peripheral vascular
disease or cardiac revascularization, and all were taking antidiabetic
Although the development of torcetrapib was halted,
researchers said two other CETP inhibitors that do not cause the adverse
effects dalcetrapib and anacetrapib are in the drug approval
In an accompanying editorial, Stephen D. Wiviott,
MD, a member of the TIMI Study Group and from the CV division at Brigham
and Womens Hospital, Harvard School of Medicine, said this analysis
may provide additional insight into the relationships between two key risk
factors for CV disease, lipids (in particular, HDL) and glycemia.
However, Wiviott said the glycemic findings from
ILLUMINATE may be due to chance, as is the case in some post hoc analyses.
With these important reductions of key surrogate
markers of the risk of CV disease, including LDL, HDL, triglycerides and
glycemia, this seems like a drug that should be widely prescribed to those at
risk for CVD. Of course, it is not now, and will never be, prescribed to our
patients for these indications. The reason for this is that, despite the
observed benefits on these key surrogates, patients treated with torcetrapib in
ILLUMINATE had 25% more CV events, including 58% more total deaths than those
treated with placebo, Wiviott wrote.
For more information:
- Barter P. Circulation. 2011;124
- Wiviott SD. Circulation. 2011;124
Disclosure: The Heart Research Institute in Sydney funded the
study and Pfizer provided statistical assistance. Dr. Wiviott said this
research for the editorial was funded by Eli Lilly, Daiichi Sankyo, Merck and
Pfizer; he also reported consulting and independent CME speaking for Eli Lilly,
Daiichi Sankyo, AstraZeneca, Angelmed, Medco, Bristol-Myers Squibb,
Ortho-McNeil and Sanofi-Aventis.