Wasehuus, Victor;
Smeijer, J David;
Ambery, Phil;
Greasley, Peter J;
Wijkmark, Emma;
Wheeler, David C;
Rossing, Peter;
(2025)
Effects of combined treatment with zibotentan and dapagliflozin compared to dapagliflozin alone in patients with diabetic and non-diabetic chronic kidney disease.
Diabetes, Obesity and Metabolism
10.1111/dom.16468.
(In press).
Preview |
PDF
Diabetes Obesity Metabolism - 2025 - Wasehuus - Final published version Effects of combined treatment with zibotentan and dapagliflozin compared to (2).pdf - Published Version Download (1MB) | Preview |
Abstract
AIMS: To evaluate whether type 2 diabetes status modifies the efficacy and safety of combining zibotentan (zibo), a selective endothelin receptor antagonist, and dapagliflozin (dapa) compared to placebo plus dapagliflozin in individuals with chronic kidney disease (CKD). METHODS AND MATERIALS: We conducted a post hoc analysis of the ZENITH-CKD trial, a multicentre 12-week, double-blind, randomized, active-controlled, phase 2b study involving 447 participants with CKD (261 with and 186 without type 2 diabetes). Participants were assigned to zibotentan (0.25 or 1.5 mg) plus dapagliflozin 10 mg or placebo plus dapagliflozin 10 mg. Changes in urinary albumin-to-creatinine ratio (UACR) and markers of fluid retention (bodyweight and B-type natriuretic peptide [BNP]) were compared in participants with and without type 2 diabetes. RESULTS: Zibo/dapa 0.25/10 mg changed UACR by -37.7% (90% CI: -40.4, -23.4) compared to placebo/dapa in participants without diabetes and by -17.9% (90% CI: -31.3, -2.0) in participants with diabetes (p-interaction 0.096). Effects of zibo/dapa 1.5/10 mg on UACR were consistent regardless of diabetes status (-34.0% (90% CI: -45.0, -20.8) vs. -33.0% (90% CI: -42.2, -22.5), p-interaction 0.921). Changes in body weight and BNP did not differ by diabetes status. Fluid retention occurred in five participants with diabetes assigned to zibo/dapa 1.5/10 mg and one participant with diabetes in the zibo/dapa 0.25/10 mg group. Fluid retention did not occur in those without diabetes in both zibo/dapa groups. With placebo/dapa, fluid retention occurred in one participant without diabetes and in none with diabetes. CONCLUSIONS: Combination therapy with zibotentan and dapagliflozin demonstrated consistent efficacy and safety across CKD patients with and without type 2 diabetes.
| Type: | Article |
|---|---|
| Title: | Effects of combined treatment with zibotentan and dapagliflozin compared to dapagliflozin alone in patients with diabetic and non-diabetic chronic kidney disease |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/dom.16468 |
| Publisher version: | https://doi.org/10.1111/dom.16468 |
| Language: | English |
| Additional information: | © 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
| Keywords: | clinical trial, diabetes complications, randomised trial, type 2 diabetes |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10210655 |
Archive Staff Only
 |
View Item |
