Do VERTIS-CV trial results question a class-effect of cardiovascular protection with sodium-glucose cotransporter 2 inhibitors?

VERTIS-CV was planned according to the Food and Drug Administration (FDA) former guidelines to assess the CV safety of new glucose-lowering drugs (recently updated to evaluate safety more broadly). Therefore, this study was originally designed and powered to show non-inferiority of ertugliflozin compared to placebo with respect to CV outcomes in high-risk patients with type 2 diabetes. From this point of view, the ‘mission’ was accomplished since VERTIS-CV results showed non-inferiority of ertugliflozin compared to placebo. However, based on previous studies showing positive effects of other SGLT2i on CV and renal outcomes, the VERTIS-CV protocol had been amended to reflect a doubling of the original sample size and inclusion of efficacy objectives for superiority.