CHICAGO: Pioglitazone slowed atherosclerosis progression

Drug reduced carotid IMT more than glimepiride in patients with type 2 diabetes.

Issue: December 2006

Treatment with pioglitazone has demonstrated significant improvements on cardiovascular markers in patients with type 2 diabetes, including the halting of atherosclerosis progression as measured by carotid intima-media thickness.

“Pioglitazone slowed the progression of mean and maximal carotid intima-media thickness compared to glimepiride,” said Theodore Mazzone, MD, FACP, professor of medicine and director of the Section of Endocrinology, Diabetes and Metabolism at the University of Illinois at Chicago. Mazzone presented the results of the Carotid Intima-Media Thickness in Atherosclerosis Using Pioglitazone (CHICAGO) trial at the American Heart Association’s Scientific Sessions 2006.

Study design

CHICAGO was a 72-week, randomized, double-blind study that enrolled 462 patients from 28 centers in the Chicago area.

Patients were randomized to 15 mg to 45 mg daily pioglitazone (n=232) or 1 mg to 4 mg daily glimepiride as an active comparator (n=230). Dosages depended on patients’ sulfonylurea use at study entry: Patients not taking sulfonylureas or low-dose sulfonylureas were assigned to 15 mg pioglitazone or 1 mg glimepiride; remaining patients were assigned 30 mg pioglitazone or 2 mg glimepiride, with all doses titrated to maintain a target fasting plasma glucose of 140 mg/dL.

The primary outcome of the study was the absolute change in average posterior-wall carotid intima-media thickness (IMT) in both the left and right carotid arteries. The secondary endpoint was absolute change in maximal carotid IMT.

The first composite clinical endpoint included cardiovascular mortality, nonfatal MI or nonfatal stroke. The second clinical endpoint included the same measures as the first as well as coronary revascularization, carotid endarterectomy or stenting, and hospitalization for unstable angina or congestive heart failure.

Subgroups for analysis were prespecified: age, sex, systolic BP, duration of diabetes, BMI, HbA1c and statin use.

The mean age of patients in the study was 60. The average duration of diabetes was 7.7 years and average HbA1c levels were 7.4%. Patients were generally well-controlled for CVD risk factors, Mazzone said.

Average carotid IMT at baseline was 0.771 mm in the pioglitazone group and 0.779 mm in the glimepiride group. Maximum carotid IMT at baseline was 1.038 mm in the pioglitazone group and 1.042 mm in the glimepiride group.

Difference in CIMT

Patients in the pioglitazone arm showed a 0.001-mm decrease in arterial thickness from baseline vs. an increase of 0.012-mm in the glimepiride arm, for a total difference of 0.013 mm between the two arms (95% CI, –0.024 to –0.002).

Patients in the pioglitazone group experienced a 0.002-mm increase in maximum carotid IMT compared with a 0.026-mm increase in patients given glimepiride, a treatment difference of 0.024 mm (95% CI, –0.042 to –0.006).

HDL levels increased by 12.8% in the pioglitazone group vs. a decrease of 1.1% in the glimepiride group, a treatment difference of 6.4 mg/dL (95% CI, 5.0 mg/dL to 7.9 mg/dL). Triglyceride levels decreased 13.5% with pioglitazone treatment vs. a 2.1% increase with glimepiride (95% CI, 24%-7.3%).

Pioglitazone reduced HbA1c levels by an average of 0.33% vs. 0.01% in the glimepiride group (95% CI, –0.52% to –0.12%).

Patients given pioglitazone gained more weight than those given glimepiride (3.2 kg vs. 1.0 kg, respectively; P<.001).

After adjudication of cardiac events, no cardiac mortality was reported. In the glimepiride group, there were 10 events (one MI, one stroke and eight coronary revascularizations); in the pioglitazone group, there were four events (three coronary revascularizations and one CHF), Mazzone said. – by Evan Young

Source: Mazzone, et al. JAMA. 2006;0296.21.joc60158-10.

This article also appeared in Today in Cardiology, a SLACK Incorporated publication.

For more information:

Mazzone T. Effect of pioglitazone compared to glimepiride on carotid intima-media thickness (CIMT) in type 2 diabetes — Results of the CHICAGO study. Presented at: American Heart Association’s Scientific Sessions 2006; Nov. 12-15, 2006; Chicago.