title: Current perspectives on cardiovascular outcome trials in diabetes.
abstract: Cardiovascular disease (CVD) is one of the most common diabetes-associated complications, as well as a leading cause for death in type 2 diabetes patients (T2D). Despite the well-known correlation between the two, up until the 2008 FDA industry guidance for licensing of new anti-hyperglycemic drugs, which required an investigation of cardiovascular outcomes (CVO) of glucose-lowering agents, only a few studies had looked into the relationship between glucose lowering drugs and cardiovascular (CV) risk. Thereafter, CVOT design has focused on non-inferiority short-term studies on high-risk patient populations aiming at capturing CV safety issues. Despite the wealth of information and useful data provided by CVOTs, this approach still suffers from certain limitations. The present review will condense the main results of the most recently completed CVOTs, reflect on the lessons learned, discuss on the issues presented by current CVOT design and offer some suggestions for improvement.
authors.affiliation: Forschergruppe Diabetes e.V., Munich, Ingolstaedter Landstrasse 1, 85764, Neuherberg (Munich), Germany. oliver.schnell@lrz.uni-muenchen.de.
authors.forename: Oliver
authors.initials: O
authors.lastname: Schnell
authors.affiliation: Cardiology Unit, Department of Medicine K2, Karolinska Institutet, 171 76, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Rydén
authors.affiliation: Forschergruppe Diabetes e.V., Munich, Ingolstaedter Landstrasse 1, 85764, Neuherberg (Munich), Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Standl
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer-IDIBAPS, Mallorca, 183, 08036, Barcelona, Spain.|IRCCS MultiMedica, Via Milanese, 300, 20099, Milan, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ceriello
mesh_terms: D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D002986:Clinical Trials as Topic / Q000379:methods*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D061214:Patient Safety; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents
keywords: CVOT; Cardiovascular risk; Cardiovascular safety; Diabetes; Non-inferiority