SGLT2 inhibitors: Salty or Just Sweet?
Abstract
• Dapagliflozin lowers blood pressure without clear effects on sodium excretion in people with T2D and preserved kidney function • Dapagliflozin did not induce prolonged changes in plasma volume, extracellular volume, and intracellular volume • Other nondiuretic-related effects cannot be ruled out in the CV protective effects conferred by SGLT2 inhibitors, including reductions in arterial stiffness, inhibition of the sympathetic nervous system, or restoration of endothelial function. • Multiple intra-kidney compensatory mechanisms are activated to counteract dapagliflozin-induced osmotic diuresis, including 1) an increase in co-peptin 2) decrease in free water clearance that facilitate maintenance of normal urinary volumes 3) a decrease in fractional urea excretion and 4) activation of RAS. • Dapagliflozin decreased blood pressure despite no clear changes in 24-hr sodium and volume excretion in patients with CKD without T2D. • Dapagliflozin activates kidney specific adaptive mechanisms to maintain body fluid and sodium balance to prevent volume depletion, including activation of RAS and stimulation of ADH release, in patients with CKD without T2D. • Kidney-active drugs do not seem to alter the effect of SGLT2 inhibitors on hard kidney endpoints in large outcome trials. • Dapagliflozin over 24 weeks provides similar clinically relevant improvements in urinary albumin- creatinine ratio (UACR), eGFR, HbA1c, and hematocrit, irrespective of treatment with RAS inhibitors at…
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