Clinical trial studies drug’s ability to prevent diabetes

Dr. Ralph DeFronzo
Dr. Ralph DeFronzo

San Antonio (Feb. 17, 2004) – The Texas Diabetes Institute, a partnership of the Health Science Center and the University Health System, is recruiting individuals for a four-year clinical trial of pioglitazone (brand name Actos) for the prevention of type 2 diabetes.

Dr. Ralph DeFronzo, professor of medicine at the Health Science Center and deputy director of the Texas Diabetes Institute, said the trial should demonstrate pioglitazone’s ability to improve the body’s sensitivity to insulin and prevent insulin-producing beta cells from dying.

Dr. DeFronzo is principal investigator for the ACT NOW Trial (Actos Now for the Prevention of Type 2 Diabetes), which will compare outcomes of pre-diabetic individuals receiving pioglitazone with those receiving a placebo.

Early in life, type 2 diabetics produce three or four times the amount of insulin produced by individuals who are not diabetic. The problem is that the body does not respond to the insulin, and the beta cells eventually start to fail.

Later in life, as the beta cells start to fail, the amount of insulin in the blood starts to fall. At this stage, even though the blood insulin levels are higher than in non-diabetic individuals, the amount of insulin isn’t enough because of the severity of the body’s resistance to insulin.

Pioglitazone is part of the thiazolidine family of medications. “Much of the basic research on this class of drug was done here,” Dr. DeFronzo said. “We were amongst the first to show that these drugs improve insulin sensitivity.”
Thiazolidine drugs also save beta cells from dying. “We believe this class of drugs cannot only improve how the tissues respond to insulin, but also improve how much insulin is made by the body, thereby preventing diabetes,” Dr. DeFronzo said.

The ACT NOW Trial will enroll patients at eight U.S. centers, including the Texas Diabetes Institute. The researchers will identify people who are pre-diabetic. Half will get pioglitazone and half placebo. Treatment will be for 39 months.

“We anticipate that 60 percent to 70 percent of the patients in the pioglitazone arm will not develop diabetes,” Dr. DeFronzo said. “If individuals are taking placebo and develop diabetes, they will receive pioglitazone.”

The researchers also believe that pioglitazone treatment, administered when people first develop diabetes, will prevent the blood glucose levels from rising and thus prevent blindness, kidney failure and nerve damage. Diabetics also are more prone to heart attacks and stroke. There is good evidence that the thiazolidines may prevent atherosclerosis, Dr. DeFronzo said.

By taking ultrasound wave readings of the subjects’ carotid arteries, the researchers will test for thickening of the artery, signaling atherosclerosis. “We believe this drug will cause regression of the atherosclerosis,” Dr. DeFronzo said.

Hispanics are at higher risk for type 2 diabetes and its complications, such as heart disease, stroke, amputations, blindness and kidney failure. The study coordinators seek to enroll large numbers of Hispanics and African Americans.

To be screened for eligibility, call (210) 358-7200. The study is looking to enroll pre-diabetics – individuals who are at high risk to develop diabetes later in life. Pre-diabetics include individuals with a strong family history of diabetes (including gestational diabetes) and individuals who are significantly overweight. There is no cost to participate, and subjects will be reimbursed for their time. Dr. DeFronzo’s group will enroll 75 to 100 patients.

Dr. DeFronzo emphasized the importance of weight loss and exercise. It’s been shown that exercise activates an important biochemical pathway to increase insulin sensitivity.

The ACT NOW trial is supported by a $7.4 million grant from Takeda Pharmaceuticals, makers of Actos.

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