Cardiovascular effects of SGLT-2 inhibitors: what we have learned from cardiovascular outcome trials and what we still need to understand

The recent results of the DECLARE-TIMI 58 trial forces a profound reflection about the cardiovascular protection conferred by SGLT-2 inhibitors. DECLARE-TIMI 58, the largest cardiovascular outcome trial in diabetes, failed to show a significant reduction in the risk of major adverse cardiovascular events (MACEs) conferred by dapagliflozin compared with placebo. However, a lower rate of hospitalization for heart failure was reported. Whilst the lack of benefits on MACE may seem in contrast with the results of previous SGLT-2 inhibitors cardiovascular outcome trials, DECLARE clearly delineates the real cardiovascular effects of SGLT-2 inhibitors, which mainly tackle heart failure. Differences in study design and population enrolled are crucial to correctly value each molecule and to translate results of clinical trials in daily clinical practise.