A study found that the diabetes drug Pioglitazone ( Actos ) reduced carotid artery intima-media thickness ( IMT ).
Patients taking Pioglitazone also experienced significant reductions in insulin resistance, C-reactive protein, a marker for inflammation, and blood pressure, all of which contribute to the overall risk for cardiovascular disease.

" These study results support the growing body of evidence that, beyond its effects on blood glucose, Pioglitazone may keep blood vessels healthy and prevent hardening of the arteries, " says lead investigator Thomas Forst of the Institute for Clinical Research and Development in Mainz, Germany. " We are encouraged by these results because the benefits seen with Pioglitazone could, theoretically, lead to an overall reduction in the incidence of heart attack and stroke for people with type 2 diabetes."

Carotid intima-media thickness occurs in the inner lining of a person's neck arteries, and is a strong indicator for cardiovascular risk because that is where cholesterol rich atherosclerotic plaque accumulates.
A thickened carotid intima-media layer correlates with not only with the presence of cardiovascular risk factors, but also with the risk of future cardiovascular events such as heart attack and stroke.
While blood pressure has long been a known predictor of heart disease, recent findings have indicated that testing CRP levels in the blood may be a new way to further assess cardiovascular disease risk.
For people with type 2 diabetes, the risk of cardiovascular disease is two to four times that of the general population, thus making this population a very high-risk group.

The study was designed to examine the effects of oral therapy with either Pioglitazone ( 45 mg/day ) or the blood glucose-lowering drug Glimepiride ( 2.7 ± 1-6 mg ) for 12 and 24 weeks, on metabolic control ( HbA1c ), insulin resistance ( homeostasis model assessment ) and carotid artery thickness ( B-mode ultrasound ).

A total of 89 patients were randomized to the Pioglitazone arm, and 84 patients to the Glimepiride arm.
The population included 66 females and 107 males with type 2 diabetes aged 62.6 ± 7.9 years, with a mean body mass index ( BMI ) of 31.8 ( generally classified as obese ).

Treatment was generally well tolerated. Despite similar improvements in metabolic control after 24 weeks, ( HbA1c: -0.8±0.9% Pioglitazone versus -0.6±0.8% Glimiperide ) carotid IMT was reduced from baseline only in the Pioglitazone group after both 12 weeks ( -0.033±0.052mm in the Pioglitazone treated patients versus -0.002±0.047mm in the Glimepiride-treated patients, p<0.01 between groups ) and after 24 weeks of treatment ( -0.054±0.059mm versus -0.011± 0.058mm, respectively, p<0.005 between groups ).

In addition, insulin resistance was significantly improved in the Pioglitazone group versus the Glimepiride group.

Changes in IMT correlated with improvement in insulin resistance were found to be independent from the improvement in metabolic control.

The Pioglitazone group also realized an improvement in CRP. In parallel, a statistically significant improvement was seen in blood pressure in the Pioglitazone group at 24 weeks, while the Glimepiride group was unchanged from baseline. The difference between blood pressure levels at 24 weeks between the Pioglitazone and Glimepiride groups was statisically significant ( p<0.01 )

Treatment with Pioglitazone was associated with a higher number of cases of increased body weight and edema. Two patients in the Pioglitazone arm experienced a clinically significant deterioration in their preexisting cardiac insufficiency.

Source: Circulation, 2005


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