Evidence map›Paper›PMID 40396470›Full record

Trial reportDiabetes, obesity & metabolism2025

Effects of combined treatment with zibotentan and dapagliflozin compared to dapagliflozin alone in patients with diabetic and non-diabetic chronic kidney disease.

Victor Wasehuus, J David Smeijer, Phil Ambery, Peter J Greasley, Emma Wijkmark, David C Wheeler, Peter Rossing, Hiddo J L Heerspink

Abstract readRandomized Controlled TrialMulticenter StudyClinical Trial, Phase II
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Trial
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Victor WasehuusSteno Diabetes Center Copenhagen, Herlev, Denmark.ORCID 0000-0003-1822-8188
J David SmeijerDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0003-1725-9927
Phil AmberyBioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0003-2978-1886
Peter J GreasleyBioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Emma WijkmarkBioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
David C WheelerCentre for Kidney and Bladder Health, University College London, London, UK.
Peter RossingSteno Diabetes Center Copenhagen, Herlev, Denmark.ORCID 0000-0002-1531-4294
Hiddo J L HeerspinkDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0002-3126-3730

Funding

AstraZeneca
6 · The paper itself

Abstract

aimsTo 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.

resultsZibo/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.

conclusionsCombination therapy with zibotentan and dapagliflozin demonstrated consistent efficacy and safety across CKD patients with and without type 2 diabetes.

Indexed as

Benzhydryl CompoundsDiabetes Mellitus, Type 2Diabetic NephropathiesEndothelin Receptor AntagonistsGlucosidesRenal Insufficiency, ChronicSodium-Glucose Transporter 2 InhibitorsAgedAlbuminuriaDouble-Blind MethodDrug Therapy, CombinationFemaleHumansHypoglycemic AgentsMaleMiddle AgedBenzhydryl CompoundsdapagliflozinEndothelin Receptor AntagonistsGlucosidesHypoglycemic AgentsSodium-Glucose Transporter 2 Inhibitorsclinical trialdiabetes complicationsrandomised trialtype 2 diabetes

Identifiers

PMID40396470
PMCPMC12232351

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.