Pioglitazone regressed CIMT in type 2 diabetes in the CHICAGO study
Carotid intima media thickness (CIMT) was significantly regressed with pioglitazone while it progressed with glimepiride, in a study of patients with type 2 diabetes over a 6-year follow-up. The CHICAGO study was presented at the Scientific Sessions of the American Heart Association and published online simultaneously in the Journal of the American Medical Association.
Dr. Theodore Mazzone, principal investigator and chief of Endocrinology, Diabetes and Metabolism at the University of Illinois at Chicago, said the results are particularly significant because the benefits were found in patients with well controlled diabetes, hypertension, and hyperlipidemia, at target levels advocated by the American Heart Association and American Diabetes Association. Further, he said that the results suggest a potentially novel mechanism for managing cardiovascular risk in patients with diabetes.
The primary endpoint of CIMT continued to increase from baseline with GML to 0.012 mm, while CMIT regressed from baseline with PIO to minus 0.001. The difference was statistically significant (p=0.017).
Patients were randomized to pioglitazone 15-45 mg/day (n=175) or glimepiride 1-4 mg/day (n=186), with initial dosing based on baseline sulfonylurea use and its dose. Drugs were titrated to maintain a fasting plasma glucose below 140 mg/dL.
The mean age of the patients was 60 years (range 45-85), 62% were men, with a mean BMI of 32. All patients had type 2 diabetes (mean duration 7.7 years), an HbA1c ≥6.5% and < 10% (mean 7.4%), without symptomatic CAD, cerebrovascular disease, peripheral arterial disease, or cardiac failure. The patient population was racially and ethnically diverse.
The mean baseline CMIT was 0.779 in the glimepiride group and 0.771 in the pioglitazone group. At the final visit, the between group difference in CMKIT was -0.013 (p=0.017). All pre-specified subgroups benefited from pioglitazone.
Parameter |
|
Mean Baseline Level |
|
|
End of study |
|
|
Treatment difference |
P value |
|
|
Pioglitazone |
Glimepiride |
|
Pioglitazone |
Glimepiride |
|
|
|
Primary Endpoint |
|
|
|
|
-0.001 mm |
+0.012 mm |
|
-0.013 mm |
P=0.02 |
Secondary Endpoint |
|
1.038 mm |
1.042 mm |
|
+0.002 mm |
+0.026 |
|
-0.024 mm |
p=0.008 |
TG |
|
178.6 mg/dL |
170.4 mg/dL |
|
-13.5% |
+2.1% |
|
15.6% |
<0.001 |
LDL-C |
|
113.8 mg/dL |
111.3 mg/dL |
|
+5.8% |
+1.0% |
|
|
P=0.012 |
Systolic blood pressure |
|
130.1 |
128.7 |
|
-2.0 mm Hg |
-0.3 mmHg |
|
|
P=0.27 |
|
Only 1 patient in the pioglitazone group and no patients in the glimepiride group developed heart failure.
HbA1c values were decreased by week 16 in the pioglitazone group and remained fairly stable through the end of the study, while there was a rapid decrease in HbA1c in the glimepiride group which gradually increased until the end of the study. No significant differences were seen between groups for HbA1c until week 48.
“If supported by additional research, these findings would indicate that pioglitazone can delay the progression of atherosclerosis in patients with diabetes,” said Mazzone. “This suggests a potentially novel mechanism for managing cardiovascular risk in patients with diabetes.”
|
