Mechanistic Study of the Systolic Blood Pressure Lowering Effect of Dapagliflozin in Type 2 Diabetes

Dapagliflozin has been shown to lower clinic systolic and diastolic blood pressure in patients with type 2 diabetes mellitus. In particular, the reduction in SBP is impressive. The effect on circadian patterns of blood pressure measured by ambulatory blood pressure monitoring has not been established. The exact mechanism(s) by which dapagliflozin lowers clinic SBP is not clear although there has been speculation that it is due to a decrease in intravascular volume secondary to the osmotic diuresis produced by the drug. However, SBP is dependent on both pulse volume and vascular stiffness (impedance to ejection).

Dapagliflozin may have a favorable effect on vascular stiffness by a reduction in blood glucose resulting in decreased proximal arterial collagen cross-linking due to non-enzymatic glycosylation of proteins.

Dapagliflozin may also have a favorable effect on vascular stiffness by increasing urinary sodium excretion. Dapagliflozin is a sodium/glucose co-transporter inhibitor and the effects on sodium excretion are not clear. Increased sodium intake is associated with an increase in vascular stiffness.

An increase in vascular stiffness has been correlated with increased cardiovascular morbidity and mortality. Thus, it is important to know if dapagliflozin has an effect on vascular stiffness.

The current "gold standard" for vascular stiffness is aortic pulse wave velocity (aPWV). Other measures of vascular stiffness include: systolic blood pressure, pulse pressure and augmentation index. Also, measurement of calculated central blood pressure provides information that may not be apparent from measurement of brachial blood pressure.