Evidence map›GLP-1 receptor agonists × kidney outcomes›PMID 28854085›Full record

Trial reportThe New England journal of medicine2017

Liraglutide and Renal Outcomes in Type 2 Diabetes.

Johannes F E Mann, David D Ørsted, Kirstine Brown-Frandsen, Steven P Marso, Neil R Poulter, Søren Rasmussen, Karen Tornøe, Bernard Zinman, John B Buse, LEADER Steering Committee and Investigators

4 registry-linked trialsOpen access · bronzeAbstract readComparative StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The New England journal of medicine, 2017. The graph read 2 numbers from its abstract, feeding 1 cell of the map, but it casts no vote: it is a later paper about NCT01179048, whose primary report (PMID 27295427) speaks for the trial. It reports registered trial NCT01179048. Cited by 527 papers, 20 of them syntheses that pooled it.

2numbers the graph read from it
0cells of the map it votes in
527citing papers in PubMed, 20 pooled it
87.5field-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.

← favours the treatmentfavours the comparator →
1 · no effect
New onset of persistent macroalbuminurialiraglutide vs placebofavours the treatment · ckd, t2dfeeds one cell of the map
HR 0.740.60 to 0.91P=0.004
This result was driven primarily by the new onset of persistent macroalbuminuria, which occurred in fewer participants in the liraglutide group than in the placebo group (161 vs. 215 patients; hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P=0.004).
FeedsGLP-1 receptor agonists×kidney outcomes

Read, but not usablea number the graph found but could not read as for or against

Renal outcomeliraglutide vs placebodirection of benefit for this outcome is not defined · ckd, t2dfeeds one cell of the map
HR 0.780.67 to 0.92P=0.003
The renal outcome occurred in fewer participants in the liraglutide group than in the placebo group (268 of 4668 patients vs. 337 of 4672; hazard ratio, 0.78; 95% confidence interval [CI], 0.67 to 0.92; P=0.003).
FeedsGLP-1 receptor agonists×kidney outcomes

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

GLP-1 receptor agonists×kidney outcomes

Does not voteOpen on the map →What to test next →

7 readable studies in this cell: 3 favour the treatment, 4 find no difference, 0 favour the comparator.

Belief with this paper
0.50contested · 2 families support, 1 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
This paper’s trial, registry resultNCT01179048 · 9,341 enrolled · 2010
HR 0.780.67 to 0.92
NCT038191533,533 enrolled · 2019
HR 0.760.66 to 0.88
NCT017204463,297 enrolled · 2013
Treatment ratio 0.780.68 to 0.89
NCT01620489279 enrolled · 2012
Estimated treatment ratio 0.980.94 to 1.02
NCT04865770106 enrolled · 2021
Treatment ratio 0.980.96 to 1.01
4 · 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.

NCT01179048 phase3completed

A Long-term, Multi-centre, International, Randomised Double-blind, Placebo-controlled Trial to Determine Liraglutide Effects on Cardiovascular Events

Ran2010Enrolled9,341Registered outcomes6Posted comparisons20ConditionsDiabetes, Diabetes Mellitus, Type 2Armsliraglutide, Placebo
PMID 28476871PMID 29947247PMID 24176437PMID 30851070PMID 29760228PMID 30508430PMID 30566004PMID 30566006PMID 30260088PMID 29903847PMID 25656058PMID 25275271other papers from this trial
Open the trial in the graph
NCT04529278 phase2unknown statusstarted 2021, after this paper: background citation

Efficacy and Tolerance of Liraglutide for Weight Loss in Obese Type 2 Diabetic Hemodialysis Patients

Ran2021Enrolled18Registered outcomes8Posted comparisons0ConditionsDiabetes Mellitus, Type 2, Hemodialysis, ObeseArmsliraglutide
PMID 29726082PMID 25526642PMID 19853906PMID 18931095PMID 30122305PMID 26283739PMID 22383694PMID 19926371PMID 24742478PMID 24911038PMID 28493926other papers from this trial
Open the trial in the graph
NCT06894784 phase3recruitingstarted 2025, after this paper: background citation

Semaglutide And Empagliflozin Combination Therapy Added To Automated Insulin Delivery In Adults With Type 1 Diabetes (SEMPA)

Ran2025Enrolled36Registered outcomes13Posted comparisons0ConditionsDiabetes Type 1ArmsIntervention Period 1: Semaglutide + Empagliflozin, Intervention Period 2: Semaglutide + Empagliflozin Placebo, Intervention Period 3: Semaglutide Placebo + Empagliflozin, Intervention Period 4: Semaglutide Placebo + Empagliflozin Placebo
PMID 20616619PMID 36942888PMID 31539622PMID 29246950PMID 27295427PMID 25388240PMID 24947583PMID 27633186PMID 30833170PMID 29397376PMID 19925391PMID 10233049other papers from this trial
Open the trial in the graph
NCT04231838 naunknown statusnot on this mapstarted 2021, after this paper: background citation

A Randomised Controlled International Multicentre Study Evaluating Changes in Metabolic Syndrome in Smokers With Type 2 Diabetes Mellitus After Switching From Tobacco Cigarettes to Combustion-Free Nicotine Delivery Systems: DIASMOKE Study

TypeinterventionalSponsorEclat Srl.Ran2021 to 2026Enrolled576ConditionsCardiovascular Risk Factor, Diabetes Mellitus, Type 2ArmsTOBACCO CIGARETTES, COMBUSTION-FREE NICOTINE DELIVERY SYSTEMS (C-F NDS)
5 · Its place in the literature

Who cites it

527 citing papers in PubMed, 20 syntheses or guidelines pooled it, 1,196 citations in OpenAlex.

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467 more citing papers are in PubMed but not listed here.

6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Johannes F E MannFrom KfH Kidney Center, Munich, and Friedrich Alexander University of Erlangen, Erlangen - both in Germany (J.F.E.M.); Novo Nordisk, Bagsvaerd, Denmark (D.D.Ø., K.B.-F., S.R., K.T.); University of Texas Southwestern Medical Center, Dallas (S.P.M.); Imperial College London, London (N.R.P.); Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto (B.Z.); and University of North Carolina School of Medicine, Chapel Hill (J.B.B.).
David D ØrstedFrom KfH Kidney Center, Munich, and Friedrich Alexander University of Erlangen, Erlangen - both in Germany (J.F.E.M.); Novo Nordisk, Bagsvaerd, Denmark (D.D.Ø., K.B.-F., S.R., K.T.); University of Texas Southwestern Medical Center, Dallas (S.P.M.); Imperial College London, London (N.R.P.); Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto (B.Z.); and University of North Carolina School of Medicine, Chapel Hill (J.B.B.).
Kirstine Brown-FrandsenFrom KfH Kidney Center, Munich, and Friedrich Alexander University of Erlangen, Erlangen - both in Germany (J.F.E.M.); Novo Nordisk, Bagsvaerd, Denmark (D.D.Ø., K.B.-F., S.R., K.T.); University of Texas Southwestern Medical Center, Dallas (S.P.M.); Imperial College London, London (N.R.P.); Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto (B.Z.); and University of North Carolina School of Medicine, Chapel Hill (J.B.B.).
Steven P MarsoFrom KfH Kidney Center, Munich, and Friedrich Alexander University of Erlangen, Erlangen - both in Germany (J.F.E.M.); Novo Nordisk, Bagsvaerd, Denmark (D.D.Ø., K.B.-F., S.R., K.T.); University of Texas Southwestern Medical Center, Dallas (S.P.M.); Imperial College London, London (N.R.P.); Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto (B.Z.); and University of North Carolina School of Medicine, Chapel Hill (J.B.B.).
Neil R PoulterFrom KfH Kidney Center, Munich, and Friedrich Alexander University of Erlangen, Erlangen - both in Germany (J.F.E.M.); Novo Nordisk, Bagsvaerd, Denmark (D.D.Ø., K.B.-F., S.R., K.T.); University of Texas Southwestern Medical Center, Dallas (S.P.M.); Imperial College London, London (N.R.P.); Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto (B.Z.); and University of North Carolina School of Medicine, Chapel Hill (J.B.B.).
Søren RasmussenFrom KfH Kidney Center, Munich, and Friedrich Alexander University of Erlangen, Erlangen - both in Germany (J.F.E.M.); Novo Nordisk, Bagsvaerd, Denmark (D.D.Ø., K.B.-F., S.R., K.T.); University of Texas Southwestern Medical Center, Dallas (S.P.M.); Imperial College London, London (N.R.P.); Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto (B.Z.); and University of North Carolina School of Medicine, Chapel Hill (J.B.B.).
Karen TornøeFrom KfH Kidney Center, Munich, and Friedrich Alexander University of Erlangen, Erlangen - both in Germany (J.F.E.M.); Novo Nordisk, Bagsvaerd, Denmark (D.D.Ø., K.B.-F., S.R., K.T.); University of Texas Southwestern Medical Center, Dallas (S.P.M.); Imperial College London, London (N.R.P.); Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto (B.Z.); and University of North Carolina School of Medicine, Chapel Hill (J.B.B.).
Bernard ZinmanFrom KfH Kidney Center, Munich, and Friedrich Alexander University of Erlangen, Erlangen - both in Germany (J.F.E.M.); Novo Nordisk, Bagsvaerd, Denmark (D.D.Ø., K.B.-F., S.R., K.T.); University of Texas Southwestern Medical Center, Dallas (S.P.M.); Imperial College London, London (N.R.P.); Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto (B.Z.); and University of North Carolina School of Medicine, Chapel Hill (J.B.B.).
John B BuseFrom KfH Kidney Center, Munich, and Friedrich Alexander University of Erlangen, Erlangen - both in Germany (J.F.E.M.); Novo Nordisk, Bagsvaerd, Denmark (D.D.Ø., K.B.-F., S.R., K.T.); University of Texas Southwestern Medical Center, Dallas (S.P.M.); Imperial College London, London (N.R.P.); Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto (B.Z.); and University of North Carolina School of Medicine, Chapel Hill (J.B.B.).
LEADER Steering Committee and Investigators
Universitätsklinikum Erlangen · DE

Funding

North Carolina Translational & Clinical Sciences Institute (NC TraCS)UL1TR001111 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BUSE, JOHN BERNARD, CAREY, TIMOTHY S · 2013 to 2017
$43.9M
NCATS NIH HHS UL1 TR001111
8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

backgroundIn a randomized, controlled trial that compared liraglutide, a glucagon-like peptide 1 analogue, with placebo in patients with type 2 diabetes and high cardiovascular risk who were receiving usual care, we found that liraglutide resulted in lower risks of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and death. However, the long-term effects of liraglutide on renal outcomes in patients with type 2 diabetes are unknown.

methodsWe report the prespecified secondary renal outcomes of that randomized, controlled trial in which patients were assigned to receive liraglutide or placebo. The secondary renal outcome was a composite of new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, end-stage renal disease, or death due to renal disease. The risk of renal outcomes was determined with the use of time-to-event analyses with an intention-to-treat approach. Changes in the estimated glomerular filtration rate and albuminuria were also analyzed.

resultsA total of 9340 patients underwent randomization, and the median follow-up of the patients was 3.84 years. The renal outcome occurred in fewer participants in the liraglutide group than in the placebo group (268 of 4668 patients vs. 337 of 4672; hazard ratio, 0.78; 95% confidence interval [CI], 0.67 to 0.92; P=0.003). This result was driven primarily by the new onset of persistent macroalbuminuria, which occurred in fewer participants in the liraglutide group than in the placebo group (161 vs. 215 patients; hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P=0.004). The rates of renal adverse events were similar in the liraglutide group and the placebo group (15.1 events and 16.5 events per 1000 patient-years), including the rate of acute kidney injury (7.1 and 6.2 events per 1000 patient-years, respectively).

conclusionsThis prespecified secondary analysis shows that, when added to usual care, liraglutide resulted in lower rates of the development and progression of diabetic kidney disease than placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .).

Indexed as

Acute Kidney InjuryAgedAlbuminuriaCreatinineDiabetes Mellitus, Type 2Diabetic NephropathiesDouble-Blind MethodFemaleFollow-Up StudiesGlomerular Filtration RateGlucagon-Like Peptide 1HumansHypoglycemic AgentsIntention to Treat AnalysisKidney Failure, ChronicLiraglutideCreatinineGlucagon-Like Peptide 1Hypoglycemic AgentsLiraglutide

Identifiers

PMID28854085
OpenAlexW2752707491

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Texttitle and abstract
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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.