SGLT2 Inhibitors and Mechanisms of Hypertension

We sought to review currently available data on the safety and efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in type 2 diabetes mellitus patients with hypertension. Inhibition of SGLT2 in the renal proximal tubule results in increased urinary glucose excretion and modest improvements of hemoglobin A1C. Treatment with any of the three currently FDA-approved SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) results in sustained systolic and diastolic blood pressure reduction, in part via minimal natriuresis and possible reductions in sympathetic tone. Recent randomized clinical trials in high cardiovascular risk patients with type 2 diabetes suggest that the unique effects of SGLT2 inhibitors on blood pressure and body weight may translate into reduced cardiovascular events and slowed kidney disease progression. However, concerns about volume depletion and acute kidney injury have been raised. SGLT2 inhibitors are viable second-line glucose-lowering agents for people with type 2 diabetes with high cardiovascular risk.