Sotagliflozin outperforms dapagliflozin for reducing salt- sensitive hypertension and kidney injury: Study

Salt-sensitive hypertension—elevated blood pressure due to excess salt consumption— affects nearly half of individuals with high blood pressure and substantially contributes to kidney disease, cardiovascular complications, and progression to kidney failure. When researchers compared selective SGLT2 inhibition (through treatment with dapagliflozin) with dual SGLT1/2 inhibition(through treatment with sotagliflozin) in a well-established rat model of salt-induced hypertension and chronic kidney disease, they found that both drugs had profound effects on slowing the progression of salt-induced hypertension.

Compared with selective SGLT2 inhibition, dual SGLT1/2 inhibition produceda greater reduction in mean arterial pressure and more effectively attenuated kidney injury, although it had no impact on blood pressure under normal-saltconditions. Sotagliflozin also reduced body weight, enhanced urinary sodiumand chloride excretion, and nearly doubled fractional glucose excretion compared with dapagliflozin. Neither treatment altered kidney function. SGLT2 inhibition modulated several metabolic pathways in a region-specific manner in the kidney, with pronounced effects on lipid metabolism and inflammatory signaling.

“Our study provides preclinical evidence supporting the expanded use of dualSGLT1/2 inhibitors beyond heart failure and diabetes, extending their potential into hypertension management, particularly in salt-sensitive patients,” said corresponding author Olha Kravtsova, PhD, of the University of South Florida. “These findings also establish a foundation for further investigation into regional kidney metabolism. Moreover, they highlight lipid and inflammatory pathways as promising therapeutic targets in the treatment of hypertension.”

Reference: Sotagliflozin outperforms dapagliflozin for reducing salt- sensitive hypertension and kidney injury in rats; American Society of Nephrology; Meeting: ASN Kidney Week.