Zibotentan-Dapagliflozin Combo Shows Promising Results in CKD Patients With and Without Diabetes: Study

The study revealed the following findings:

• Low-dose zibotentan (0.25 mg) combined with dapagliflozin reduced UACR by 37.7% in patients without diabetes.
• The same combination led to a 17.9% reduction in UACR in patients with diabetes.
• The stronger response in non-diabetic patients was not statistically significant.
• High-dose zibotentan (1.5 mg) with dapagliflozin resulted in similar UACR reductions (~34%) in diabetic and non-diabetic patients.
• There was no significant interaction between diabetes status and treatment effect at the higher dose.
• No notable differences were observed in body weight or BNP changes based on diabetes status.
• Fluid retention occurred only in diabetic patients receiving the higher zibotentan dose.
• No cases of fluid retention were seen in non-diabetic patients receiving zibotentan.
• The combination therapy was generally well-tolerated across all patient groups.

Despite these promising findings, the authors emphasized that this was a post hoc analysis of a trial not specifically designed to compare patients based on diabetes status. Therefore, they suggest that the results be interpreted cautiously and viewed as hypothesis-generating. Moreover, the trial's 12-week duration limits any conclusions about long-term outcomes.

To address these limitations, ongoing trials like ZENITH-HP and ZODIAC are expected to offer further clarity. The ZENITH-HP trial has recruited over 1,500 CKD patients with and without diabetes, while the ZODIAC study is evaluating the individual and combined effects of zibotentan and dapagliflozin in greater detail.

"The analysis supports the potential utility of zibotentan-dapagliflozin combination therapy in CKD management across diverse patient groups, offering a promising approach that appears unaffected by diabetes status," the researchers concluded.

Reference:

https://doi.org/10.1111/dom.16468