Effects of combined treatment with zibotentan and dapagliflozin compared to dapagliflozin alone in patients with diabetic and non-diabetic chronic kidney disease
A post hoc analysis of the ZENITH-CKD trial showed adding the endothelin receptor antagonist zibotentan to dapagliflozin reduced albuminuria in CKD whether or not patients had type 2 diabetes, with fluid retention occurring mainly in those with diabetes at the higher dose.
Study design
A post hoc analysis of ZENITH-CKD, a 12-week, double-blind, randomized, active-controlled phase 2b trial of 447 participants with CKD (261 with and 186 without type 2 diabetes), comparing zibotentan (0.25 or 1.5 mg) plus dapagliflozin 10 mg against placebo plus dapagliflozin 10 mg.
Key findings
Zibotentan/dapagliflozin 1.5/10 mg reduced urinary albumin-to-creatinine ratio by about 33-34% versus placebo/dapagliflozin regardless of diabetes status (p-interaction 0.92). At the lower 0.25 mg dose the reduction was larger in those without diabetes (-37.7%) than with diabetes (-17.9%).
Safety
Changes in body weight and BNP did not differ by diabetes status. Fluid retention occurred in five participants with diabetes on the higher zibotentan dose and one on the lower dose, but in none of the participants without diabetes.
Clinical implications
Combining a selective endothelin receptor antagonist with an SGLT2 inhibitor provided consistent albuminuria-lowering across diabetic and non-diabetic CKD, supporting combination therapy while indicating fluid-retention risk is concentrated among patients with diabetes.
Category
Research
Source
Diabetes, Obesity & Metabolism
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