Cardiovascular safety trials

Cardiovascular (CV) safety trials in type 2 diabetes (T2DM) are a bit like London buses; you wait for what seems like an age and then two of them come along at once. So it was at the American Diabetes Association (ADA) meeting in June where the results of the TECOS and ELIXA studies were presented.

TECOS is the third study to report on the CV safety of a gliptin, following on from the EXAMINE (alogliptin) and SAVOR-TIMI 53 (saxagliptin) studies in September 2013. Whilst these studies confirmed CV safety of the two agents in terms of the primary endpoint (major adverse cardiovascular events or ‘MACE’), they raised the possibility of heart failure as a risk of gliptin therapy. In SAVOR-TIMI, there was a significant increase in the number of hospitalisations for heart failure in patients receiving saxagliptin; a similar but non-significant signal was seen for alogliptin.  Fortunately, the TECOS study, which randomised more than 14,000 patients to sitagliptin or placebo, had hospitalisation due to heart failure as an adjudicated end-point and so the lack of any signal for this outcome is a major reassurance. Furthermore, in a study specifically designed to exclude a drug-related increase in CV risk (rather than any impact of glycaemic control), there was absolutely convincing confirmation of safety.

ELIXA is perhaps the more interesting study, being the first to report on the CV safety of a GLP-1RA injectable therapy (lixisenatide). This group of more than 6,000 were extremely high risk, having recently experienced an acute coronary syndrome, but had very well controlled blood pressure and lipids at enrolment, along with high antiplatelet use. Once again, CV safety was confirmed with no signal for heart failure (a secondary endpoint for this study).

And so the bandwagon rolls on with the next CV safety study to report being the EMPA-REG OUTCOME with yet another class of anti-diabetic drugs under the spot-light (the SGLT-2 inhibitors). Who would bet against a similar result?

Professor Steve Bain