Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: a systematic review and meta-analysis

This review of 6 regulatory submissions (n=37,525) and 57 trials (n=33,385) found that sodium-glucose cotransporter-2 inhibitors reduced the risk of cardiovascular adverse events (RR=0.84; 95%CI 0.75-0.95), as well as cardiovascular death, heart failure and death from any cause.

The authors note that the results were driven by findings for empagloflozin (the EMPA-REG OUTCOME trial contributed three quarters of the cardiovascular events in the analysis), and that currently this is the only sodium-glucose cotransporter-2 inhibitor (SGLT2I) for which data from a dedicated long-term cardiovascular safety trial have been reported.  They also report that adverse events were more difficult to quantify compared to efficacy, and that the effects of individual drugs in the class seem to differ in some safety outcomes and that results from ongoing trials will be crucial to substantiate findings across the drug class.

A related editorial discusses this paper.  It highlights the current uncertainty in relation to risk of cardiovascular disease with some of the newer antidiabetic agents, and potential implications of new and emerging evidence of SGLT2Is