Surrogate cardiovascular outcomes with sodium-glucose co-transporter-2 inhibitors in women: An updated meta-analysis

The burden of cardiovascular disease morbidity and mortality among women with type 2 diabetes mellitus remains high, despite the improvement in therapeutic management over the recent years. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have revolutionized treatment of cardiovascular disease in subjects with diabetes. However, previous meta-analyses of cardiovascular outcome trials failed to prove a significant effect on surrogate cardiovascular outcomes among female participants. Therefore, we sought to update these results, by incorporating data from the most recently published trials. We pooled available data from all available trials (EMPA-REG OUTCOME, DECLARE-TIMI 58, VERTIS CV, DAPA-HF, EMPEROR-Reduced), except for the CANVAS trial. In the present updated meta-analysis we document that SGLT-2 inhibitors do not confer a significant decrease in the risk for major adverse cardiovascular events among women; however, they provide significant results in terms of reduction in the risk for cardiovascular death or hospitalization for heart failure, primarily driven by the results observed in the heart failure with reduced ejection fraction population. Better representation of women in future trials will provide further insights into the question whether there are true gender differences in the cardiovascular efficacy with this drug class.