Sodium-glucose Co-transporter 2 Inhibitors and Blood Pressure Reduction among Patients with Diabetes, Cardiovascular Disease, Chronic Kidney Disease

The remarkable reductions in cardiovascular events and the blunting of the decline in kidney function observed in clinical trials of patients with diabetes, cardiovascular disease, and/or chronic kidney disease treated with sodium-glucose co-transporter 2 (SGLT2) inhibitors are accompanied by a modest reduction in systolic (2–5 mm Hg) and diastolic (0.5–2.5 mm Hg) blood pressure. Blood pressure reduction occurs across a spectrum of blood pressure elevations, possibly including those with resistant hypertension, many of whom are already taking a variety of antihypertensive drugs. SGLT2 inhibitors appear to lower blood pressure to a greater extent in hypertensive Black and Asian individuals than White individuals. Mechanisms by which SGLT2 inhibitors likely contribute to blood pressure reduction and other cardiovascular and kidney benefits involve a variety of neuroendocrine, kidney, and hemodynamic systems. Some of these components include osmotic diuresis and natriuresis with a consequent decline in both interstitial and intravascular volume, weight reduction, a reduction in arterial stiffness, cardiac ventricular remodeling, loss of salt sensitivity, a decrease in uric acid concentrations, and a complicated interaction with the renin-angiotensin-aldosterone and sympathetic nervous systems. This review will provide an update on mechanisms purported to contribute to blood pressure reduction and the cardiovascular and kidney benefits observed with this the class of agents.