- Since 2008 the FDA has required demonstration of the cardiovascular safety of new glucose-lowering agents.
- The FDA established an acceptable level for estimated increased cardiovascular risk. The upper limit of the 95% confidence interval of cardiovascular risk should be <1.3 based on a combination of pre- and post-marketing studies, e.g. meta-analysis of phase 2 and 3 studies or a combination of phase 3 studies and a cardiovascular outcomes trial (CVOT). If statistical non-inferiority vs. placebo or comparator is confirmed testing for superiority is appropriate.
- Recent landmark trials – EMPA-REG OUTCOME, LEADER and SUSTAIN – have provided evidence for reduction in cardiovascular events in high risk patients with type 2 diabetes for empagliflozin, liraglutide, and semaglutide, respectively.
- Prior to embarking on large and expensive CVOTs, early phase evaluations may help provide an indication of a diabetes drug’s potential cardiovascular risk thereby informing development decisions.