Impact of the U.S. Food and Drug Administration Cardiovascular Assessment Requirements on the Development of Novel Antidiabetes Drugs

Lingering questions related to cardiovascular (CV) safety of type 2 diabetes treatments resulted in new U.S. Food and Drug Administration (FDA) regulations requiring careful assessment of CV risk. These new requirements will provide the medical community with robust data to estimate CV risk associated with new therapeutic agents. To meet these requirements, phase 2 and 3 development programs will need to be larger and more comprehensive and will include high-risk patients. In addition, it is likely that most (if not all) newly approved drugs will be required to conduct post-approval CV safety outcome studies. The purpose of this article is to review the drivers for the new FDA requirements and how these new requirements will affect the development of novel antidiabetes drugs. The goals of antidiabetes treatment are to forestall the metabolic effects of high glucose levels and to prevent microvascular and macrovascular complications. Compelling data in type 2 diabetic patients support the conclusion that improved long-term glycemic control reduces the risk of microvascular complications (1,2). Based on several large outcome studies (e.g., the Diabetes Control Complications Trial and the UK Prospective Diabetes Study [UKPDS]), glycosylated hemoglobin (HbA1c) was established as a surrogate biomarker of glycemic control and therapeutic goals were set accordingly (3). Cardiovascular disease is the leading cause of death in patients with type 2 diabetes; more than 60% die of CV disease, and an even greater proportion have serious CV-related complications. Diabetes is associated with a two- to fourfold increase in the risk of coronary heart disease and death (4). Patients with type 2 diabetes who have not had a myocardial infarction (MI) have a risk of infarction similar to that of nondiabetic patients who have had a prior MI (5–7). Pooled data from patients with acute coronary syndrome (ACS) in …

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