Diabetes affects more than 20 million people in the United States, and this number continues to rise due to the obesity epidemic and widespread physical inactivity. Though cardiovascular disease and stroke account for approximately two-thirds of deaths in people with diabetes, long-term cardiovascular trials have not been a part of the approval process in the development of diabetes drugs.

Testifying before the Food and Drug Administration (FDA) Endocrinologic and Metabolic Drugs Advisory Committee on behalf of The Endocrine Society, Dr. Robert Vigersky, president-elect of the Society and director of the Diabetes Institute at the Walter Reed Health Care System and professor of medicine at the Uniformed Services University of the Health Sciences, offered an approach that addresses the conundrum of encouraging the development of safe and effective drugs without imposing requirements that hinder such activities.

"Though large and costly studies would likely inhibit the development of helpful drugs, the FDA, patients, and their physicians should have as much information as possible in order to make an informed decision about whether or not the benefits outweigh the risks of taking any medication," said Dr. Vigersky. "The timing of this available information may be the solution to this challenge."

Dr. Vigersky outlined a two-stage approach to be considered in the approval process for all new diabetes medications. He said studies should be designed to capture both blood glucose and cardiovascular end-points, as well as both adverse clinical endpoints, including all-cause mortality, fatal and non-fatal heart attacks, and stroke and beneficial clinical outcomes such as delay in onset of renal failure, retinopathy, or neurologic damage.

A drug showing appropriate glycemic effects without an adverse short-term cardiovascular outcome would achieve "conditional" approval, said Dr. Vigersky. At some agreed-upon future time, the clinical macrovascular results would be evaluated and final approval granted. The approval status would be included in the labeling.

"Improving macrovascular outcomes should not be required for approval since this benefit would need to be balanced against the overall adverse effects," said Dr. Vigersky. "However, worse macrovascular outcomes would be grounds to rescind approval or to substantially alter the label."
 

Because of the additional expenses such a study would incur, additional years of market exclusivity for the drug might be a reasonable means to offset the costs, said Dr. Vigersky.

Dr. Vigersky also told the Committee that The Endocrine Society suggests that the FDA commission a study by an independent third party such as the Institute of Medicine to evaluate and make recommendations about this pivotal issue.

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Founded in 1916, The Endocrine Society is the world's oldest, largest, and most active organization devoted to research on hormones and the clinical practice of endocrinology. Today, The Endocrine Society's membership consists of over 14,000 scientists, physicians, educators, nurses and students in more than 80 countries. Together, these members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Md. To learn more about the Society, and the field of endocrinology, visit our web site at www.endo-society.org.