title: Evaluating the Cardiovascular Safety of New Medications for Type 2 Diabetes: Time to Reassess?
abstract: The U.S. Food and Drug Administration (FDA) issued a Guidance for Industry in 2008 defining preapproval and postapproval requirements for the demonstration of cardiovascular safety for all new medications developed for glycemic management in type 2 diabetes. Seventeen large, prospective, randomized, controlled clinical trials involving more than 140,000 subjects thus far have been completed or are ongoing in accordance with this guidance. All five of the completed trials, involving three different drug classes, have met their primary objective to exclude an unacceptable level of ischemic cardiovascular risk as defined in the FDA guidance. Additionally, one trial found an increased risk of hospitalization for heart failure, and another demonstrated decreases in cardiovascular mortality and hospitalization for heart failure. Given that a heightened risk of cardiovascular ischemic events has not been demonstrated across several classes of new diabetes drugs, we believe it is time for the scientific community and the FDA to consider a more targeted approach to what is, in effect, a global cardiovascular safety trial requirement for all new type 2 diabetes medications in development.
authors.affiliation: Department of Medicine, Alpert Medical School and Department of Health Services, Policy & Practice, School of Public Health, Brown University, and Ocean State Research Institute, Providence VA Medical Center, Providence, RI robert_j_smith@brown.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Smith
authors.affiliation: Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA.
authors.forename: Allison B
authors.initials: AB
authors.lastname: Goldfine
authors.affiliation: Division of Cardiology, University of Colorado School of Medicine, and CPC Clinical Research, Aurora, CO.
authors.forename: William R
authors.initials: WR
authors.lastname: Hiatt
mesh_terms: D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D023381:Endpoint Determination; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D007004:Hypoglycemic Agents