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

Abstract

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.

Effects of empagliflozin versus placebo on cardiac sympathetic activity in acute myocardial infarction patients with type 2 diabetes mellitus: the EMBODY trial

“…Taken together, the results of the present study were comparable with those of previous studies [ 1 – 3 ]. The early initiation of SGLT-2 inhibitor therapy should be considered in patients with T2D and established CVD [ 50 ].…”

The association between sodium-glucose cotransporter 2 inhibitors and incident dementia: A nationwide population-based longitudinal cohort study

“…[7][8][9] Many studies have also demonstrated that the use of sodium-glucose cotransporter 2 (SGLT2) inhibitor results in good glycemic control and low rate of diabetic complications. [10][11][12] However, the association between SGLT2 inhibitor and ID remains unclear. Therefore, we conducted a retrospective cohort study to explore the relationship between SGLT2 inhibitors and ID in the general Taiwanese population.…”

Effect of sodium-dependent glucose transporter inhibitors on glycated hemoglobin A1c after 24 weeks in patients with diabetes mellitus

“…A persistently elevated level of HbA1c increases the risk of vascular complications, such as coronary disease, heart attack, stroke, heart failure, kidney failure, blindness, erectile dysfunction, neuropathy, gangrene, gastroparesis, and short-term complications of surgery such as poor wound healing. [ 9 , 10 ]…”

“…Specific drugs include dapagliflozin (DAPA), canagliflozin (CANA), empagliflozin (EMPA), ertugliflozin (ERTU), and sotagliflozin (SOTA). [ 9 , 10 ] SGLT inhibitors are commonly used as second-line hypoglycemic agents in clinical practice. [ 11 ]…”