A New Era in the Management of Type 2 Diabetes: Is Cardioprotection at Long Last a Reality?

The EMPA-REG OUTCOME and the LEADER trials have revealed a new era in the management of type 2 diabetes. The SGLT2 inhibitor empagliflozin demonstrated a lower rate of the primary composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke compared to placebo. Liraglutide, a GLP-1 analogue, succeeded to demonstrate reduction on a composite outcome including first occurrence of cardiovascular death, nonfatal myocardial infarction or non-fatal stroke. These two medications act through different mechanisms and has consequently shown different patterns of cardiovascular benefit. In one hand, empagliflozin showed an earlier effect compared to those observed using liraglutide. On the other hand, the difference between empagliflozin and placebo was driven by a significant reduction in death from cardiovascular causes, with and striking disconnect showing no significant between-group difference in the risk of myocardial infarction or stroke. In contrast, liraglutide reduced consistently all components of the composite endpoint. Based on the different temporal pattern of achieving clinical benefit one might flirt with the idea that liraglutide seems to provide a chronic "protection" that better fits in a longer metabolic effect with an impact in the progression of atherosclerosis, whilst empagliflozin provides an acute effect compatible with an immediate hemodynamic action. After years going from "bench to bedside" in order to discover the holy grail of cardioprotection, these 2 new studies suggest that we may have reached this state and it is time to go from "bed back to bench side" to understand the mechanisms of this potential paradigm shift.