ADA 2009: Pioglitazone Slows Progression of Carotid Atherosclerosis

Martha Kerr

June 09, 2009

June 9, 2009 (New Orleans, Louisiana) — A substudy of ACTOS Now, a diabetes prevention trial comparing pioglitazone (Actos, Takeda Pharmaceuticals) with placebo on risk and incidence of diabetes development, showed that active treatment with the thiazolidinedione slowed the rate of progression of carotid artery intima media thickness (CIMT) by 38% during a 3-year study period.

Peter D. Reaven, MD, from the Phoenix Veterans Affairs HealthCare System in Arizona, and colleagues at 7 ACTOS Now study sites performed serial carotid artery ultrasound over the course of 39 months in 393 patients with impaired glucose tolerance who had been randomized to pioglitazone 45 mg daily or placebo.

At baseline, average age was 53 years (±12), 54% were female, average body mass index was 33.2 kg/m2 (±5.3), and average hemoglobin A1c was 5.4% (±0.4%).

Dr. Reaven told attendees here at the American Diabetes Association (ADA) 69th Scientific Sessions that "pioglitazone slowed the rate of CIMT progression . . . and this anti-atherogenic effect persisted over nearly 3 years."

The annual rate of change in CIMT was 38% lower in the pioglitazone group than in the placebo group (mean progression, 0.0055 vs 0.0089 mm/year; P = .025).

Results Persisted Even After Adjustment

"One notable finding was that the results were unchanged even after subjects that developed diabetes during the study were excluded," Dr. Reaven said, "indicating that differential rates of CIMT progression were not simply a consequence of elevated glucose."

"The annual rates of CIMT change were linear up to 4.1 years, indicating that the relative benefits of pioglitazone were persistent over the study's duration," Dr. Reaven reported.

Rates of CIMT change were unaltered, even after adjustment for baseline standard cardiovascular disease risks factors, indicating that the effects of pioglitazone on glucose-lowering "were more modest" than its effects on progression of atherosclerosis.

"While not significant, there was a trend toward greater benefit for those with more adverse risk factors," the Phoenix investigator added.

"These data support the concept that use of pioglitazone therapy early in the evolution of diabetes may have beneficial effects on cardiovascular disease," Dr. Reaven said.

Findings Reinforce That Pioglitazone Prevents Macrovascular Disease

"The findings reinforce the notion that pioglitazone prevents macrovascular disease," echoed R. Paul Robertson, MD, the ADA's president of Medicine and Science, and an endocrinologist at Swedish Medical Center in Seattle, Washington.

"These patients were all prediabetic, with symptoms of the metabolic syndrome, including impaired glucose tolerance, and they were overweight," Dr. Robertson told Medscape Diabetes & Endocrinology in an interview after Dr. Reaven's presentation.

"We should be treating all patients with prediabetes with early aggressive treatment," Dr. Robertson advised. "I certainly do [it] in my practice."

He added that "by waiting, we are  . . . wasting time and allowing subclinical disease progression. We might even be able to head off disease with early treatment."

ACTOS Now was funded by Takeda Pharmaceuticals. Dr. Reaven receives research support from Amylin Pharmaceuticals, Eli Lilly & Company, Merck & Company, and Takeda Pharmaceuticals. Dr. Robertson receives support from Merck.

American Diabetes Association (ADA) 69th Scientific Sessions: LB-15. Presented June 8, 2009.

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