Following the results of the EMPA-REG OUTCOME trial with empagliflozin, is it possible to speak of a class effect?

Abstract

Francisco Javier Ampudia‑Blasco,1 Irene Romera,2 Bernat Ariño,3 Ramón Gomis4 1Endocrinology and Nutrition Department, Clinic University Hospital Valencia, Valencia, Spain; 2Eli Lilly and Company España, Madrid, Spain; 3Boehringer Ingelheim España, Barcelona, Spain; 4Endocrinology Department, Hospital Clinic Barcelona, Barcelona, Spain Background: The recently published cardiovascular outcomes data for the first sodium–glucose cotransporter 2 (SGLT2) inhibitor, empagliflozin, have shown cardiovascular safety and additional benefits in patients with type 2 diabetes and established cardiovascular disease. Empagliflozin showed lower rates of death from cardiovascular causes or from any causes and lower hospitalization rates from heart failure compared with placebo, both in addition to standard care. This commentary discusses the existence of a possible class effect considering the available evidence described for other SGLT2 inhibitors. Main text: Empagliflozin, dapagliflozin and canagliflozin share the same mechanism of action, and it is a plausible hypothesis that some of the benefits of empagliflozin treatment could also be expected from other SGLT2 inhibitors. However, the rapid and persistent occurrence of cardiovascular benefits observed with empagliflozin and the different results shown by the three inhibitors in meta-analyses of some of their respective Phase II and III trials might suggest another possible mechanism of action, perhaps related to the different selectivity to inhibit SGLT-2 and other SGLT family members that these compounds present. Conclusion: There is still lack of evidence to answer whether the cardiovascular benefits observed with empagliflozin in the EMPA-REG OUTCOME study could be seen as a “class effect”, which is also attributable to dapagliflozin and canagliflozin. Keywords: cardiovascular, outcome studies, SGLT2 inhibitors, empagliflozin, dapagliflozin, canagliflozin

Keywords

• cardiovascular
• outcome studies
• SGLT2 inhibitors
• empagliflozin
• dapagliflozin
• canagliflozin.