VERTIS-CV Results 'Disappoint,' Raise More Questions

The VERTIS-CV trial results, presented at this year's virtual American Diabetes Association (ADA) Scientific Sessions, raise more questions than they answer.

Before we dive into interpreting the implications of these results and the purported cardiovascular (CV) benefits of SGLT2 inhibitors, let's review some commonsense caveats:

• We still need to wait for the peer-reviewed publication from VERTIS-CV.

• CV outcome trials (CVOTs) are not head-to-head, with numerous study differences, making comparisons difficult.

Nonetheless, the presenters of the VERTIS-CV session asserted that the overall results of this new study are in line with other SGLT2-inhibitor outcome trials, based on a new meta-analysis combining their results with EMPA-REG, CANVAS, CREDENCE, and DECLARE-TIMI 58.

But can clinical decisions be based solely on meta-analyzing such heterogeneous trials? Or should we first consider the overall neutral results (primary and all secondary endpoints) of the CVOT in question? And then, as the next step, compare like-vs-like CVOTs before meta-analyzing a variety of CVOTs and chronic kidney disease outcome trials?

Why did they jump straightaway to comparing and combining apples and oranges?

Comparing Like-vs-Like CVOTs

VERTIS-CV is similar to EMPA-REG in multiple ways. Both trials had similar baseline characteristics and background glucose-lowering and cardioprotective medications, which is expected, given that the enrollment criteria for both studies were limited to secondary prevention populations with