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.

Keywords: CVOT; Cardiovascular risk; Cardiovascular safety; Diabetes; Non-inferiority.

Fig. 1

Confidence interval (CI) bars indicated by FDA guideline. Shown are five examples of hazard ratios (HR) and the upper limit of the 95 % CI of a development plan and regulatory consequences of each outcome. S superiority, NI non-inferiority, I inferiority, UP underpowered