Dapagliflozin: Cardiovascular Safety and Benefits in Type 2 Diabetes Mellitus

Abstract

Sodium-glucose co-transporter 2 inhibitors (SGLT2is) such as dapagliflozin, canagliflozin, and empagliflozin, are a promising new therapy in the treatment of type 2 diabetes mellitus (T2DM). SGLT2is can effectively reduce hyperglycemia thus improving glycemic control and they offer some beneficial effects on the cardiovascular (CV) system which can benefit patients with heart failure in addition toT2DM. The United States Food and Drug Administration requires new diabetes mellitus therapies to show a CV safety profile. Empagliflozin was the first SGLT2i that, when added to the standard of care for patients withT2DM at high risk for CV events, showed improved CV outcomes including reduced deaths from CV causes. Evidence also exists in favor of dapagliflozin for use in patients with T2DM with CV risk factors and heart failure. This review focuses on the effects, safety, and benefits of dapagliflozin on the CV system. Clinical trials have shown that dapagliflozin improves glycemic control without variation. It is safe and well-tolerated in the general population including older patients and those with high-risk CV factors or preexisting CV disease. There may be a renal protective role by an unknown mechanism. Dapagliflozin also lowers blood pressure due to its natriuresis effect. It improves levels of visceral fat and reduces body weight, and thus ameliorates metabolic syndrome. Dapagliflozin reduces oxidative stress and may delay atherosclerosis. Recent findings indicate SGLT2is may also reduce the atrial natriuretic peptide levels. Additional trials are required to validate these benefits and further evaluate if these are class effects. Trials such as DECLARE-TIMI58 are ongoing to evaluate the CV outcomes of dapagliflozin. More research is needed to design better antihyperglycemic regimes with clinical benefits in addition to good glycemic control.