Diabetes Drug Slows Clogging of Arteries

Actos better at fighting plaque build-up than older medication, study finds

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HealthDay Reporter

MONDAY, March 31, 2008 (HealthDay News) -- The diabetes drug Actos is better than another diabetes drug, Amaryl, at slowing clogging of the arteries in patients with both type 2 diabetes and cardiovascular disease.

The Cleveland Clinic researchers behind the new findings say this is the first time that a diabetes medication has been shown to slow atherosclerosis, giving doctors new insight into which drugs may be most effective and safest for this group of patients.

"As we go forward, the study tells us that we must do comparative effectiveness trials looking at different diabetes strategies," study author Steve Nissen, chairman of the department of cardiovascular medicine at Cleveland Clinic, said Monday. "We can't just focus on pricking your finger, getting blood sugar down. The goal in diabetes therapy is to prevent complications, and the most feared complication is heart disease, which will kill 75 percent of all diabetics. I'm thrilled with results."

Another expert hailed the results.

"The biggest news here is that pioglitazone [Actos] appears safe, does not increase cardiovascular risk, and may even reduce it," said Dr. Robert Scott III, an assistant professor of internal medicine at the Texas A&M Health Science Center College of Medicine and senior staff cardiologist with Scott&White in Temple, Texas. "It looks safe to use in people with coronary artery disease, and it is well-tolerated. We may need another trial to see how it helps, but at least it doesn't hurt, and that was our biggest concern."

The findings are published in the April 2 issue of the Journal of the American Medical Association and were released Monday to coincide with a presentation at the American College of Cardiology annual meeting, in Chicago. The research was funded by Takeda Pharmaceuticals North America Inc., which makes Actos.

Individuals with type 2 diabetes are particularly susceptible to atherosclerosis, as evidenced by the fact that 75 percent of this group eventually die of cardiovascular disease.

Amaryl (glimepiride) belongs to a class of drugs known as sulfulonylureas, which have been prescribed for decades. Actos, along with its cousin Avandia, is a thiazolidinedione, a relatively new class of diabetes drugs.

Both Actos and Avandia appear to increase the risk of heart failure (the entire class now carries a black-box warning to that effect), but Avandia has been associated with an increased risk of heart attack, while Actos has been linked with a reduced risk of negative cardiovascular outcomes.

"Both are associated with heart failure, but there were increased deaths [with Avandia]," said Dr. Stanley Mirsky, an endocrinologist with Lenox Hill Hospital in New York City and co-author of the Diabetes Survival Guide.

For this study, 543 patients with both coronary disease and type 2 diabetes were randomized to receive either Amaryl or Actos for 18 months. Actos works by making the body more sensitive to insulin, while Amaryl works by spurring the body to produce more insulin. All participants were also taking medications for heart disease.

Progression of atherosclerosis was measured by intravascular ultrasonography in the 360 patients who actually completed the study.

One measure found a 0.73 increase in plaque in the Amaryl group versus a 0.16 decrease in the Actos group. A second measure found a 0.64 increase for Amaryl and a 0.06 decrease for Actos.

The study was not designed to measure actual clinical endpoints, meaning cardiovascular events or death.

The authors stated that the exact mechanisms for the decreases associated with Actos were unclear, although several biomarkers linked to atherosclerosis progression were impacted by the drug, including a 16 percent increase in HDL or "good" cholesterol, a 15 percent reduction in triglyceride levels, and a 45 percent drop in C-reactive protein (CRP) levels.

It's also not clear if the benefits associated with Actos extend to other medications in that class of drugs.

An accompanying editorial found the results "reassuring."

"You've got to take into consideration the benefit of preventing heart attacks may be greater than the few people who get heart failure," Mirsky said.

More information

Visit the American Heart Association for more on atherosclerosis.

SOURCES: Steve Nissen, chairman, department of cardiovascular medicine, Cleveland Clinic, Ohio; Robert Scott III, M.D., Ph.D., assistant professor, internal medicine, Texas A&M Health Science Center College of Medicine, and senior staff cardiologist, Scott & White, Temple, Texas; Stanley Mirsky, M.D., endocrinologist, Lenox Hill Hospital, associate clinical professor, metabolic disease, Mount Sinai School of Medicine, New York City, and co-author, Diabetes Survival Guide; March 31, 2008, presentation, American College of Cardiology annual meeting, Chicago; April 2, 2008, Journal of the American Medical Association

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