Evidence map›Paper›PMID 34009708›Full record

ArticleDiabetes, obesity & metabolism2021

Potential kidney protection with liraglutide and semaglutide: Exploratory mediation analysis.

Johannes F E Mann, John B Buse, Thomas Idorn, Lawrence A Leiter, Richard E Pratley, Søren Rasmussen, Tina Vilsbøll, Benjamin Wolthers, Vlado Perkovic

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetes, obesity & metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 6 pooled it
9.7field-weighted citation impact, top 1% 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.

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

59 citing papers in PubMed, 6 syntheses or guidelines pooled it, 101 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Cardiovascular Safety Profile of Semaglutide and Variations by Sex, Race, and Kidney Function: A Systematic Review and Meta-analysis.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2025 · on this map
    Pooled it
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  6. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2022
    Guideline
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  11. Effect of semaglutide on kidney function across different levels of baseline HbA1c, blood pressure, body weight and albuminuria in SUSTAIN 6 and PIONEER 6.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
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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

9 authors at 7 institutions in 6 countries.

Johannes F E MannDepartment of Nephrology, Friedrich Alexander University of Erlangen, Erlangen, Germany.ORCID 0000-0002-3154-5332
John B BuseUniversity of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Thomas IdornNovo Nordisk A/S, Søborg, Denmark.
Lawrence A LeiterLi Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Richard E PratleyAdventHealth Translational Research Institute, Orlando, Florida, USA.
Søren RasmussenNovo Nordisk A/S, Søborg, Denmark.
Tina VilsbøllSteno Diabetes Centre Copenhagen, Gentofte, Denmark.
Benjamin WolthersNovo Nordisk A/S, Søborg, Denmark.
Vlado PerkovicThe George Institute, UNSW, Sydney, New South Wales, Australia.
Novo Nordisk (Denmark) · DKFriedrich-Alexander-Universität Erlangen-Nürnberg · DESt. Michael's Hospital · CATranslational Research Institute for Metabolism and Diabetes · USUniversity of Copenhagen · DKUniversity of North Carolina at Chapel Hill · USUNSW Sydney · AU

Funding

Re-Entry Supplement: Investigation of Oral Microbial Enzymes for the Detection and Treatment of Periodontal DiseaseUL1TR002489 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BUSE, JOHN BERNARD, SHAHEEN, NICHOLAS J · 2018 to 2022
$48.6M
Pilot & Feasibility ProgramP30DK124723 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI P Darrell Neufer · 2020 to 2026
$11.0M
CIHRNCATS NIH HHS UL1 TR002489NIDDK NIH HHS P30 DK124723
6 · The paper itself

Abstract

aimsTo investigate whether effects on chronic kidney disease risk factors could explain the apparent reduction in kidney outcomes (composite of macroalbuminuria, doubling of serum creatinine, renal replacement therapy, or renal death), primarily driven by changes in albuminuria, after treatment with the glucagon-like peptide-1 receptor agonists (GLP-1RAs) liraglutide and semaglutide in patients with type 2 diabetes in the LEADER and SUSTAIN 6 trials. MATERIALS AND

methodsWe evaluated the mediation effect of glycated haemoglobin (HbA1c), systolic blood pressure (BP), and body weight on the kidney effects of GLP-1RAs. Diastolic BP, haemoglobin, heart rate, low-density lipoprotein and total cholesterol, and white blood cell count were also investigated. The mediation effect was estimated by the novel Vansteelandt statistical method. Subgroups with estimated glomerular filtration rate (eGFR) <60 and ≥60 mL/min/1.73 m

resultsWe observed that HbA1c mediated 25% (95% confidence interval [CI] -7.1; 67.3) and 26% (95% CI noncalculable), and systolic BP 9% (95% CI 2.8; 22.7) and 22% (95% CI noncalculable) of kidney effects of GLP-1RAs in LEADER and SUSTAIN 6, respectively. Small or no mediation was observed for the other parameters; for example, body weight mediated 9% (95% CI -7.9; 35.5) in the former and did not mediate effects in the latter study. Mediation by HbA1c was greater in patients with eGFR ≥60 mL/min/1.73 m

conclusionsOur results suggest that HbA1c and systolic BP may moderately mediate kidney benefits of liraglutide and semaglutide, with all other variables having a small to no effect. Potential kidney benefits may be driven by other mediators or potentially by direct mechanisms.

Indexed as

Diabetes Mellitus, Type 2LiraglutideGlucagon-Like Peptide-1 ReceptorGlucagon-Like PeptidesHumansHypoglycemic AgentsKidneyMediation AnalysisSemaglutideGlucagon-Like Peptide-1 ReceptorGlucagon-Like PeptidesHypoglycemic AgentsLiraglutideSemaglutidechronic kidney diseaseglucagon-like peptide-1 receptor agonistkidney mediationliraglutidesemaglutidetype 2 diabetes

Identifiers

PMID34009708
PMCPMC8453827
OpenAlexW3163402894

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.