Evidence map›Paper›PMID 39656268›Full record

Trial reportDiabetologia2025

Sex differences in the efficacy of angiotensin receptor blockers on kidney and cardiovascular outcomes among individuals with type 2 diabetes and diabetic kidney disease: post hoc analyses of the RENAAL and IDNT trials.

Sieta T de Vries, Michelle J Pena, Sok Cin Tye, Sanne A E Peters, Daniël H van Raalte, Clare Arnott, Adriaan A Voors, Peter G M Mol, Petra Denig, 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 NCT00308347 (A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Renal Protective Effects of Losartan in Patients With Non-insulin Dependent Diabetes Mellitus and Nephropathy), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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.

NCT00308347 phase3completednot on this map

A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Renal Protective Effects of Losartan in Patients With Non-insulin Dependent Diabetes Mellitus and Nephropathy

TypeinterventionalSponsorOrganon and CoRan1996 to 2001Enrolled1,513ConditionsType 2 Diabetes, NephropathyArmsMK0954, losartan / Duration of Treatment: mean 3.4 years, Placebo / Duration of Treatment: mean 3.4 years
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Observational
  3. Review
  4. 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

10 authors.

Sieta T de VriesDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0001-6090-2434
Michelle J PenaDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0003-3340-2893
Sok Cin TyeDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0002-7286-1745
Sanne A E PetersJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0003-0346-5412
Daniël H van RaalteDiabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VU University Medical Center, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0003-2894-6124
Clare ArnottThe George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0001-9370-9913
Adriaan A VoorsDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0002-5417-4415
Peter G M MolDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0002-4262-3180
Petra DenigDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0002-7929-4739
Hiddo J L HeerspinkDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. h.j.lambers.heerspink@umcg.nl.ORCID http://orcid.org/0000-0002-3126-3730

Funding

Innovative Medicines Initiative 2 Joint Undertaking & Horizon Europe Research and Innovation Actions 101095146Innovative Medicines Initiative 2 Joint Undertaking & Horizon Europe Research and Innovation Actions grant agreement No 115974
6 · The paper itself

Abstract

aims/hypothesisOur aim was to assess sex differences in the efficacy of angiotensin receptor blockers (i.e. losartan and irbesartan) on kidney and cardiovascular outcomes in individuals with type 2 diabetes and diabetic kidney disease.

methodsData from the Angiotensin II Antagonist Losartan Study (RENAAL) and Irbesartan type II Diabetic Nephropathy Trial (IDNT) were used. The kidney outcome was time to first event of end-stage kidney disease or doubling of serum creatinine. The cardiovascular outcome was time to first event of a composite of stroke, myocardial infarction, cardiovascular death or hospitalisation for heart failure. Sex differences were assessed by a sex × treatment interaction term in Cox proportional hazards models.

resultsIncluded were 1737 male participants and 924 female participants. The beneficial effect of angiotensin receptor blockers on the kidney outcome was similar between male and female participants (HR in male participants 0.72 [95% CI 0.59, 0.86] vs HR in female participants 0.86 [95% CI 0.69, 1.06]; sex × treatment interaction HR 1.19 [95% CI 0.89, 1.59]). For the cardiovascular outcome, angiotensin receptor blockers lowered the risk in male but not in female participants (HR in male participants 0.81 [95% CI 0.69, 0.95] vs HR in female participants 1.11 [95% CI 0.88, 1.40]; sex × treatment interaction HR 1.37 [95% CI 1.03, 1.82]). CONCLUSIONS/

interpretationThis study in individuals with type 2 diabetes and diabetic kidney disease suggests that the beneficial effects of angiotensin receptor blockers are similar in male and female participants for the kidney outcome but not for the cardiovascular outcome. More attention to sex differences in angiotensin receptor blockers' efficacy and underlying mechanisms of differences in response is needed.

trial registrationClinialTrials.gov NCT00308347.

Indexed as

Angiotensin Receptor AntagonistsCardiovascular DiseasesDiabetes Mellitus, Type 2Diabetic NephropathiesAgedBiphenyl CompoundsFemaleHumansIrbesartanKidneyLosartanMaleMiddle AgedSex FactorsTreatment OutcomeAngiotensin Receptor AntagonistsBiphenyl CompoundsIrbesartanLosartanAngiotensin receptor blockersCardiovascular outcomeDiabetic kidney diseaseKidney outcomeRenin–angiotensin systemSex differences

Identifiers

PMID39656268

What Socratic holds

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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 Socratic graph.