SGLT-2 inhibitors are the groups of drugs most recently introduced in the clinical practice. The first two published studies
of cardiovascular safety and prevention with SGLT-2 inhibitors EMPA-REG OUTCOME (empagliflozin) and CANVAS
(canagliflozin) observed the following:
A positive group effect of SGLT-2 inhibitors was observed in relationship to the primary composite outcome, hospitalizations
for heart failure (HF) and progression of chronic kidney disease.
Non-significant effect of canagliflozin on all-cause and cardiovascular mortality is probably related to a lower cardiovascular
basal risk of patients included in CANVAS in comparison with patients included in EMPA-REG OUTCOME. The
treatment with SGLT-2 inhibitors is thus indicated for the prevention of major cardiovascular events, hospitalizations for
HF and progression of chronic kidney disease in patients with type 2 diabetes and both very high (EMPA-REG OUTCOME,
mortality 30/1,000 patient-years) and high (CANVAS, mortality 20/1,000 patient-years) baseline cardiovascular risk.
The treatment with canagliflozin in CANVAS was associated with a doubling of risk of predominantly distal lower limb
amputations. Post-hoc analysis from the EMPA-REG OUTCOME study did not find this effect to have been associated
with the empagliflozin treatment.