Evidence map›Paper›PMID 39661119›Full record

Trial reportDiabetologia2025

Sex differences in response to the endothelin receptor antagonist atrasentan in individuals with type 2 diabetes and chronic kidney disease: a post hoc analysis of the SONAR trial.

J David Smeijer, Sieta T de Vries, Donald E Kohan, Fan Fan Hou, Hiddo J L Heerspink

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Diabetologia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01858532 (A Randomized, Multicountry, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of Atrasentan on Renal Outcomes in Subjects With Type 2 Diabetes and Nephropathy. SONAR), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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.

NCT01858532 phase3terminatednot on this map

A Randomized, Multicountry, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of Atrasentan on Renal Outcomes in Subjects With Type 2 Diabetes and Nephropathy. SONAR: Study Of Diabetic Nephropathy With Atrasentan

TypeinterventionalSponsorAbbVieRan2013 to 2018Enrolled5,107ConditionsDiabetic NephropathyArmsAtrasentan, Placebo
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

5 authors.

J David SmeijerDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0003-1725-9927
Sieta T de VriesDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0001-6090-2434
Donald E KohanDivision of Nephrology, School of Medicine, University of Utah Health, Salt Lake City, UT, USA.ORCID http://orcid.org/0000-0002-3981-2941
Fan Fan HouDivision of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, Guangzhou, China.ORCID http://orcid.org/0000-0003-3117-7418
Hiddo J L HeerspinkDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. h.j.lambers.heerspink@umcg.nl.ORCID http://orcid.org/0000-0002-3126-3730

Funding

HORIZON Research and Innovation Actions 101095146Innovative Medicines Initiative 115974
6 · The paper itself

Abstract

aims/hypothesisIn the Study Of diabetic Nephropathy with AtRasentan (SONAR), the endothelin receptor antagonist (ERA) atrasentan slowed progression of chronic kidney disease (CKD) in individuals with type 2 diabetes. Pre-clinical research suggests sex-based differences in the endothelin system might influence the efficacy and safety of atrasentan. We therefore assessed the effects of atrasentan in men and women participating in SONAR.

methodsSONAR was a double-blind, placebo-controlled trial that compared atrasentan 0.75 mg/day with placebo in individuals with type 2 diabetes and CKD (eGFR 25-75 ml/min per 1.73 m

resultsAmong 3668 randomised participants, 946 (25.8%) were female. Atrasentan significantly reduced the risk of the composite kidney outcome in female participants (HR 0.46 [95% CI 0.28, 0.76]) but not in male participants (HR 0.83 [95% CI 0.65, 1.05]; p value for interaction 0.032). Atrasentan compared with placebo reduced eGFR decline to a greater extent in female than in male participants (treatment effect difference between male vs female participants -0.99 ml/min per 1.73 m CONCLUSIONS/

interpretationAtrasentan showed greater kidney protection in female than in male participants but also induced more heart failure events in the female participants. These data suggest that sex-specific dosing regimens may be considered to optimise ERA treatment.

trial registrationClinicalTrials.gov NCT01858532.

Indexed as

AtrasentanDiabetes Mellitus, Type 2Diabetic NephropathiesEndothelin Receptor AntagonistsPyrrolidinesRenal Insufficiency, ChronicAgedDouble-Blind MethodFemaleGlomerular Filtration RateHumansMaleMiddle AgedSex FactorsAtrasentanEndothelin Receptor AntagonistsPyrrolidinesAtrasentanClinical trialDiabetic kidney diseaseEndothelin receptor antagonistSex

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Registered trials

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.