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  • Title: Rationale for the Early Use of Sodium-Glucose Cotransporter-2 Inhibitors in Patients with Type 2 Diabetes.
    Author: Handelsman Y.
    Journal: Adv Ther; 2019 Oct; 36(10):2567-2586. PubMed ID: 31444707.
    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. People with type 2 diabetes (T2D) are at risk of developing complications, including macrovascular [cardiovascular disease (CVD), strokes, and heart failure (HF)] and microvascular [chronic kidney disease (CKD) and damage to the eyes and nerves] conditions. Reduction of blood sugar (glucose) levels (glycemic control) can prevent or halt these complications. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a class of glucose-lowering drugs that improve glycemic control, reduce CV (cardiovascular) risk factors such as being overweight and having high blood pressure, and have a low risk of hypoglycemia (low blood sugar levels). Health care providers who treat people with T2D sometimes add SGLT-2 inhibitors after initial treatment with metformin alone. Recently, clinical trials and real-world studies in patients with T2D have shown that SGLT-2 inhibitors (empagliflozin, canagliflozin, and dapagliflozin) reduced the risk of CV events, CV death, and hospitalization for HF and reduced worsening of kidney disease. Although the reduction in CV events with SGLT-2 inhibitor treatment was greatest for patients who already had CVD, the risk was also reduced in those without CVD. Reductions in death from CV causes or hospitalization for HF and kidney events were similar for patients with or without CVD. Some updated treatment guidelines for T2D, therefore, recommend early use of SGLT-2 inhibitors in patients with T2D, not only those with established CVD. This review describes the reasons for starting early treatment with SGLT-2 inhibitors when the potential benefit may be greatest, providing protection against CV events, hospitalization for HF, and progression of CKD.
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