Evidence map›Paper›PMID 37716952›Full record

ArticleCardiovascular diabetology2023

Insulin resistance, kidney outcomes and effects of the endothelin receptor antagonist atrasentan in patients with type 2 diabetes and chronic kidney disease.

J David Smeijer, Donald E Kohan, Peter Rossing, Ricardo Correa-Rotter, Adrian Liew, Sydney C W Tang, Dick de Zeeuw, Ron T Gansevoort, Wenjun Ju, Hiddo J Lambers Heerspink

2 registry-linked trialsOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular diabetology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 15 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 2 pooled it
5.5field-weighted citation impact, top 3% of its field
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.

NCT01356849 phase2completednot on this map

RADAR: Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With AtRasentan - A Phase 2b, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Safety and Efficacy

TypeinterventionalSponsorAbbVie (prior sponsor, Abbott)Ran2011 to 2012Enrolled149ConditionsChronic Kidney Disease, Diabetic NephropathyArmsAtrasentan, Placebo
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

15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 25 citations in OpenAlex.

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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

10 authors at 9 institutions in 8 countries.

J David SmeijerDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Donald E KohanDivision of Nephrology, University of Utah Health, Salt Lake City, UT, USA.
Peter RossingSteno Diabetes Center Copenhagen, Herlev, Denmark.
Ricardo Correa-RotterNational Medical Science and Nutrition Institute Salvador Zubirán, Mexico City, Mexico.
Adrian LiewMount Elizabeth Novena Hospital, Singapore, Singapore.
Sydney C W TangDivision of Nephrology, Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong.
Dick de ZeeuwDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Ron T GansevoortDepartment of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Wenjun JuDepartment of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA.
Hiddo J Lambers HeerspinkDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. h.j.lambers.heerspink@umcg.nl.
University Medical Center Groningen · NLInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán · MXMount Elizabeth Novena Hospital · SGSteno Diabetes Center · DKThe George Institute for Global Health · AUUniversity of Groningen · NLUniversity of Hong Kong · HKUniversity of Michigan–Ann Arbor · USUniversity of Utah · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundInsulin resistance (IR) is a pathophysiologic hallmark of type 2 diabetes and associated with the presence of chronic kidney disease (CKD). Experimental studies suggest that endothelin-1 increases IR. We assessed the association between IR and cardio-renal outcomes and the effect of the selective endothelin receptor antagonist atrasentan on IR in patients with type 2 diabetes and CKD.

methodsWe used data from the RADAR and SONAR trials that recruited participants with type 2 diabetes and CKD [eGFR 25-75 mL/min/1.73 m², urine albumin-to-creatinine ratio of 300-5000 mg/g]. IR was calculated using the homeostatic model assessment (HOMA-IR). The association between HOMA-IR and the pre-specified cardio-renal outcomes was assessed using multivariable Cox proportional hazards regression, and effects of atrasentan on HOMA-IR by a linear mixed effect model.

resultsIn the SONAR trial, each log-unit increase in HOMA-IR was associated with an increased risk of the composite cardio-renal outcome [hazard ratio 1.32 (95%CI 1.09,1.60; p = 0.004)], kidney outcome [hazard ratio 1.30 (95%CI 1.00,1.68; p-value = 0.048)], and the kidney or all-cause mortality outcome [hazard ratio 1.25 (95%CI 1.01,1.55; p-value = 0.037)]. After 12 weeks treatment in the RADAR trial (N = 123), atrasentan 0.75 mg/day and 1.25 mg/day compared to placebo reduced HOMA-IR by 19.1 (95%CI -17.4, 44.3) and 26.7% (95%CI -6.4, 49.5), respectively. In the SONAR trial (N = 1914), atrasentan 0.75 mg/day compared to placebo reduced HOMA-IR by 9.6% (95%CI 0.6, 17.9).

conclusionsMore severe IR is associated with increased risk of cardio-renal outcomes. The endothelin receptor antagonist atrasentan reduced IR.

trial registrationRADAR trial (Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With AtRasentan): NCT01356849. SONAR trial (The Study Of Diabetic Nephropathy With AtRasentan) NCT01858532.

Indexed as

Diabetes Mellitus, Type 2Insulin ResistanceRenal Insufficiency, ChronicAtrasentanEndothelin Receptor AntagonistsHumansKidneyAtrasentanEndothelin Receptor AntagonistsAtrasentanChronic kidney diseaseEndothelin receptor antagonistInsulin resistanceType 2 diabetes

Identifiers

PMID37716952
PMCPMC10505320
OpenAlexW4386801601

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.