dapagliflozin + zibotentan

The combination of dapagliflozin and zibotentan is an investigational oral therapy for chronic kidney disease (CKD), particularly in patients with proteinuria or albuminuria. Dapagliflozin is a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor that reduces glucose reabsorption in the kidneys, leading to diuretic effects and delayed progression of CKD. Zibotentan is a highly selective endothelin A receptor antagonist that blocks the action of endothelin-1, a potent vasoconstrictor implicated in inflammation and vascular dysfunction; this results in reduced vasoconstriction, decreased inflammation, improved kidney blood flow, and reduced albuminuria. The combination leverages complementary mechanisms—zibotentan’s effect on endothelin pathways and dapagliflozin’s SGLT2 inhibition—to provide enhanced reduction in urinary albumin-to-creatinine ratio (UACR) compared to either agent alone. Clinical studies have shown that adding dapagliflozin can mitigate the fluid retention risk associated with zibotentan monotherapy[1][2][5][8].

Other names

zibotentan/dapagliflozin