title: Impact of cardiovascular outcomes on the development and approval of medications for the treatment of diabetes mellitus.
abstract: All medications currently approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes mellitus are indicated to improve glycemic control. Since 1995, FDA has used HbA1c as the primary basis for approval of these therapies because a reduction in blood glucose lessens the symptoms of hyperglycemia and lowering of HbA1c has been shown to reduce the risk for some of the chronic complications of diabetes. Despite evidence of clinical benefit with therapies that reduce HbA1c, concerns have been raised that some diabetes medications may increase cardiovascular risk in a patient population that is already vulnerable to cardiovascular disease. Therefore, FDA convened a public advisory committee meeting to discuss the role of cardiovascular assessment in the pre-approval and post-approval settings for medications developed for the treatment of type 2 diabetes. After considering the advisory panel's recommendations and other data, FDA published a guidance document requesting evidence showing that new treatments for type 2 diabetes do not result in an unacceptable increase in cardiovascular risk. This review article begins by summarizing the events leading up to publication of this guidance. Subsequent sections discuss the guidance itself as well as general considerations for implementing the new cardiovascular recommendations. The new approach to developing medications for the treatment of type 2 diabetes will lead to evaluation in patients more representative of those who will use these therapies, if approved, and will help healthcare providers make informed decisions when choosing a medication within the growing treatment armamentarium for type 2 diabetes.
authors.affiliation: Division of Metabolism and Endocrinology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993-0002, USA. hylton.joffe@fda.hhs.gov
authors.forename: Hylton V
authors.initials: HV
authors.lastname: Joffe
authors.forename: Mary H
authors.initials: MH
authors.lastname: Parks
authors.forename: Robert
authors.initials: R
authors.lastname: Temple
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000517:prevention & control; D002986:Clinical Trials as Topic / Q000592:standards; D003920:Diabetes Mellitus / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D017277:Drug Approval / Q000379:methods*; D005188:False Negative Reactions; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D012107:Research Design / Q000592:standards; D012306:Risk; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin