Type 2 diabetes is a major risk factor for cardiovascular disease,1,2 and the presence of both type 2 diabetes and cardiovascular disease increases the risk of death.3 Evidence that glucose lowering reduces the rates of cardiovascular events and death has not been convincingly shown,4-6 although a modest cardiovascular benefit may be observed after a prolonged follow-up period.7 Furthermore, there is concern that intensive glucose lowering or the use of specific glucose-lowering drugs may be associated with adverse cardiovascular outcomes.8 Therefore, it is necessary to establish the cardiovascular safety benefits of glucose-lowering agents.9
Inhibitors of sodium–glucose cotransporter 2 reduce rates of hyperglycemia in patients with type 2 diabetes by decreasing renal glucose reabsorption, thereby increasing urinary glucose excretion.10 Empagliflozin is a selective inhibitor of sodium glucose cotransporter 211 that has been approved for type 2 diabetes.12 Given as either monotherapy or as an add-on therapy, the drug is reported to reduce glycated hemoglobin levels in patients with type 2 diabetes, including those with stage 2 or 3a chronic kidney disease.13-20 Furthermore, empagliflozin is associated with weight loss and reductions in blood pressure without increases in heart rate.13-20 Empagliflozin also has favorable effects on markers of arterial stiffness and vascular resistance,21 visceral adiposity,22 albuminuria,20 and plasma urate.13-19 Empagliflozin has been associated with an increase in levels of both low-density lipoprotein (LDL)14 and high-density lipoprotein (HDL) cholesterol.13-16 The most common side effects of empagliflozin are urinary tract infection and genital infection.12
In the EMPA-REG OUTCOME trial, we examined the effects of empagliflozin, as compared with placebo, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high risk for cardiovascular events who were receiving standard care.
Type 2 diabetes is a major risk factor for cardiovascular disease,1,2 and the presence of both type 2 diabetes and cardiovascular disease increases the risk of death.3 Evidence that glucose lowering reduces the rates of cardiovascular events and death has not been convincingly shown,4-6 although a modest cardiovascular benefit may be observed after a prolonged follow-up period.7 Furthermore, there is concern that intensive glucose lowering or the use of specific glucose-lowering drugs may be associated with adverse cardiovascular outcomes.8 Therefore, it is necessary to establish the cardiovascular safety benefits of glucose-lowering agents.9Inhibitors of sodium–glucose cotransporter 2 reduce rates of hyperglycemia in patients with type 2 diabetes by decreasing renal glucose reabsorption, thereby increasing urinary glucose excretion.10 Empagliflozin is a selective inhibitor of sodium glucose cotransporter 211 that has been approved for type 2 diabetes.12 Given as either monotherapy or as an add-on therapy, the drug is reported to reduce glycated hemoglobin levels in patients with type 2 diabetes, including those with stage 2 or 3a chronic kidney disease.13-20 Furthermore, empagliflozin is associated with weight loss and reductions in blood pressure without increases in heart rate.13-20 Empagliflozin also has favorable effects on markers of arterial stiffness and vascular resistance,21 visceral adiposity,22 albuminuria,20 and plasma urate.13-19 Empagliflozin has been associated with an increase in levels of both low-density lipoprotein (LDL)14 and high-density lipoprotein (HDL) cholesterol.13-16 The most common side effects of empagliflozin are urinary tract infection and genital infection.12In the EMPA-REG OUTCOME trial, we examined the effects of empagliflozin, as compared with placebo, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high risk for cardiovascular events who were receiving standard care.
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