CHICAGO -- In a head-to-head trial with the sulfonylurea Amaryl (glimepiride), Actos (pioglitazone), a thiazolidinedione, appeared to slow the progression of a marker for atherosclerosis in patients with type 2 diabetes, researchers reported here.
CHICAGO, Nov. 14 -- In a head-to-head trial with the sulfonylurea Amaryl (glimepiride), Actos (pioglitazone), a thiazolidinedione, appeared to slow the progression of a marker for atherosclerosis in patients with type 2 diabetes, researchers reported here.
After 72 weeks of treatment, the carotid intima-media thickness (CIMT) -- a marker of atherosclerosis -- was narrowed by 0.001 mm in the Actos arm versus an increase of 0.012 mm in the Amaryl arm, said Theodore Mazzone, M.D., of the University of Chicago.
This was an absolute difference of 0.013 mm, which was significant (P=0.02), said Dr. Mazzone, the principal investigator of the CHICAGO trial (Carotid Intima-Media Thickness in Atherosclerosis Using Pioglitazone). It was a prospective, randomized, double-blind, comparator-controlled, multicenter study conducted from October 2003 to May 2006 in a multiracial and multiethnic population at 28 clinical sites in Chicago.
Dr. Mazzone reported the results of the trial at the late-breaking clinical trials session at the American Heart Association meeting. The results were published simultaneously online by the Journal of the American Medical Association.
There were no differences in clinical symptoms or events between the groups.
The trial enrolled 462 men and women ages 45 to 85 with type 2 diabetes. They were randomized to Actos 15 to 45 mg daily or Amaryl at 1 to 4 mg.
Among the findings:
The slowing of CIMT progression was observed in all Actos treated patients, regardless of age, gender, obesity, hypertension, duration of diabetes, or glucose control, he said.
Moreover the benefit was observed irrespective of whether the patient was using a statin, Dr. Mazzone said.
Asked whether the statistically significant, but microscopic, CIMT benefit was clinically apparent, Dr. Mazzone said "extrapolating these differences to a change in clinical events is not always possible."
However, he pointed out that CIMT is recognized as an indicator of risk for stroke or myocardial infarction.
But when asked if the results suggested that Actos should be used in pre-diabetic patients, Dr. Mazzone said the data "do not support use of Actos in prediabetes."
Last month, a Cochrane review faulted the Actos clinical trial series for relying on surrogate endpoints in 21 of 22 trials.
The PROactive study reported last year did have a hard endpoint. It was time to all cause mortality, nonfatal myocardial infarction, stroke, acute coronary syndrome, endovascular or surgical intervention on coronary or leg arteries, or amputation above the ankle. But the trial did not meet this endpoint.
In PROactive the secondary endpoint of death from any cause, MI, or stroke was significant favoring Actos.
The CHICAGO trial was funded by Takeda Global Research and Development, Lincolnshire, Ill. Dr. Mazzone said he was a paid consultant or received speaking honoraria from Amylin Pharmaceuticals, Merck & Co., Novartis Pharmaceuticals, Pfizer Pharmaceutical Company, and Takeda Global Research and Development.