Rationale for the Early Use of Sodium-Glucose Cotransporter-2 Inhibitors in Patients with Type 2 Diabetes

Diabetes-related complications including cardiovascular disease, heart failure (HF), chronic kidney disease, retinopathy, and neuropathy are associated with a high burden of disease. Early initiation of glucose-lowering therapy in patients with type 2 diabetes to achieve glycemic control is important for reduction of not only microvascular risk but also of CV (cardiovascular) risk. Clinical studies have indicated that early achievement of glycemic targets is likely to have the greatest effect on preventing microvascular and macrovascular complications. In addition to improvements in glycemic control and CV risk factors, CV outcomes trials (CVOTs) of empagliflozin (EMPA-REG OUTCOME), canagliflozin (CANVAS), and dapagliflozin (DECLARE–TIMI 58) showed significant glucose-independent reductions in the risk of major adverse CV events and/or hospitalization for HF, as well as reductions in the risk of kidney disease progression, versus placebo. These CVOTs and a renal outcomes study of canagliflozin (CREDENCE) support the early initiation of sodium-glucose cotransporter (SGLT)-2 inhibitors to potentially provide the most benefit toward glycemic control and CV and renal risk. Thus, current treatment recommendations include the early addition of SGLT-2 inhibitor therapy, not only in patients with established CVD, HF, and/or CKD but also in the general population of patients with T2D. Funding: AstraZeneca.