The sodium–glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin is safe and does not increase the rate of adverse cardiovascular events in patients with type 2 diabetes mellitus, according to the results of the DECLARE–TIMI 58 trial presented at the AHA Scientific Sessions 2018. The findings are consistent with those from previous trials on canagliflozin and empagliflozin.

A total of 17,160 patients with diabetes (40.6% with established atherosclerotic cardiovascular disease and 59.4% with multiple cardiovascular risk factors) were randomly assigned to receive dapagliflozin or placebo and followed up for a median of 4.2 years. Dapagliflozin was noninferior to placebo for the occurrence of major adverse cardiovascular events (MACE; defined as cardiovascular death, myocardial infarction or ischaemic stroke), which was the primary safety outcome. For the co-primary efficacy outcomes, dapagliflozin did not reduce the rate of MACE compared with placebo (8.8% versus 9.4%) but did reduce the rate of cardiovascular death or hospitalization for heart failure (4.9% versus 5.8%; HR 0.83, 95% CI 0.73–0.95, P = 0.005), mainly driven by a significantly lower rate of hospitalization for heart failure (HR 0.73, 95% CI 0.61–0.88). The rate of renal events was 4.3% with dapagliflozin and 5.6% with placebo (HR 0.76, 95% CI 0.67–0.87).

Collectively, SGLT2 inhibitors seem to have more robust and consistent effects on prevention of heart failure and renal outcomes than on atherosclerotic events, which is consistent with their mechanism of action in the kidneys and promotion of glycosuria.

“Current international guidelines for the management of diabetes have focused on the use of SGLT2 inhibitors in patients with atherosclerotic cardiovascular disease,” comment the authors. “These new data suggest that in patients without established atherosclerotic cardiovascular disease, SGLT2 inhibitors can prevent serious clinical events, particularly hospitalization for heart failure.”