Evidence map›GLP-1 receptor agonists × cardiovascular events›PMID 39211948›Full record

Trial reportEuropean heart journal2025

Cardiovascular outcomes with semaglutide by severity of chronic kidney disease in type 2 diabetes: the FLOW trial.

Kenneth W Mahaffey, Katherine R Tuttle, Mustafa Arici, Florian M M Baeres, George Bakris, David M Charytan, David Z I Cherney, Gil Chernin, Ricardo Correa-Rotter, Janusz Gumprecht and 9 more

Abstract readRandomized Controlled TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European heart journal, 2025. The graph read 1 number from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. Cited by 21 papers, 6 of them syntheses that pooled it.

1number the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 6 pooled it
–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.

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

Cardiovascular eventscomparator not stated · ascvd, t2dfeeds one cell of the map
HR 0.820.68 to 0.98P = .03
Semaglutide reduced CV death/MI/stroke by 18% [hazard ratio (HR) 0.82 (95% confidence interval 0.68-0.98); P = .03], with consistency across estimated glomerular filtration rate categories, urine albumin-to-creatinine ratio levels, and KDIGO risk classification (all P-interaction > .13).
FeedsGLP-1 receptor agonists×cardiovascular events

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×cardiovascular events

No readable resultOpen on the map →What to test next →

13 readable studies in this cell: 7 favour the treatment, 2 find no difference, 4 favour the comparator.

Belief with this paper
0.50contested · 7 families support, 3 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
NCT0399313226,774 enrolled · 2018
HR 1.010.91 to 1.11
NCT0357459717,604 enrolled · 2018
HR 0.800.72 to 0.89
NCT013949529,901 enrolled · 2011
HR 0.880.79 to 0.99
NCT039143269,651 enrolled · 2019
HR 0.860.77 to 0.96
NCT011790489,341 enrolled · 2010
HR 0.870.78 to 0.97
NCT038191533,533 enrolled · 2019
HR 0.760.66 to 0.88
NCT017204463,297 enrolled · 2013
HR 0.740.58 to 0.95
NCT026927163,183 enrolled · 2017
HR 0.790.57 to 1.11
Liraglutide in Acute Minor Ischemic Stroke or High-Risk Transient Isch…PMID 41182740 · 1,708 enrolled · 2019
OR 1.951.28 to 3.00
NCT05564039282 enrolled · 2022
OR 20.48.40 to 49.8
Effects of Semaglutide With or Without Concomitant Mineralocorticoid R…PMID 40730031 · 2025
HR 0.790.68 to 0.92

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

5 · Its place in the literature

Who cites it

21 citing papers in PubMed, 6 syntheses or guidelines pooled it.

  1. Pooled it
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  7. Review
  8. Biologics for cardiovascular diseases: from bench to bedside.Signal transduction and targeted therapy · 2026
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6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

19 authors.

Kenneth W MahaffeyStanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, 300 Pasteur Drive, Grant S-102, Stanford, Palo Alto, CA 94305, USA.
Katherine R TuttleDivision of Nephrology, University of Washington School of Medicine, Seattle, WA, USA.
Mustafa AriciDepartment of Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Florian M M BaeresNovo Nordisk A/S, Søborg, Denmark.
George Bakris
David M CharytanDepartment of Medicine, New York University Grossman School of Medicine, New York, NY, USA.
David Z I CherneyDivision of Nephrology, University of Toronto, Toronto, ON, Canada.
Gil CherninKaplan Medical Center, Hebrew University of Jerusalem, Rehovot, Israel.
Ricardo Correa-RotterNational Institute of Medical Sciences and Nutrition, Salvador Zubirán, Mexico City, Mexico.
Janusz GumprechtDepartment of Clinical and Molecular Medicine, Medical University of Silesia, Katowice, Poland.
Thomas IdornNovo Nordisk A/S, Søborg, Denmark.
Giuseppe PuglieseDepartment of Clinical and Molecular Medicine, La Sapienza University, Rome, Italy.ORCID 0000-0003-1574-0397
Ida Kirstine Bull RasmussenNovo Nordisk A/S, Søborg, Denmark.
Søren RasmussenNovo Nordisk A/S, Søborg, Denmark.
Peter RossingSteno Diabetes Center Copenhagen, Herlev, Denmark.ORCID 0000-0002-1531-4294
Ekaterina SokarevaNovo Nordisk A/S, Søborg, Denmark.
Johannes F E MannKfH Kidney Centre, Munich, Germany.
Vlado PerkovicFaculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
Richard PratleyAdventHealth Translational Research Institute, Orlando, FL, USA.ORCID 0000-0002-2912-1389

Funding

Novo Nordisk A/S
8 · The paper itself

Abstract

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

BACKGROUND AND

aimsIn the FLOW trial, semaglutide reduced the risks of kidney and cardiovascular (CV) outcomes and death in participants with type 2 diabetes and chronic kidney disease (CKD). These prespecified analyses assessed the effects of semaglutide on CV outcomes and death by CKD severity.

methodsParticipants were randomized to subcutaneous semaglutide 1 mg or placebo weekly. The main outcome was a composite of CV death, non-fatal myocardial infarction (MI), or non-fatal stroke (CV death/MI/stroke) as well as death due to any cause by baseline CKD severity. CKD was categorized by estimated glomerular filtration rate < or ≥60 mL/min/1.73 m2, urine albumin-to-creatinine ratio < or ≥300 mg/g, or Kidney Disease Improving Global Outcomes (KDIGO) risk classification.

resultsThree thousand, five hundred and thirty-three participants were randomized with a median follow-up of 3.4 years. Low/moderate KDIGO risk was present in 242 (6.8%), while 878 (24.9%) had high and 2412 (68.3%) had very high KDIGO risk. Semaglutide reduced CV death/MI/stroke by 18% [hazard ratio (HR) 0.82 (95% confidence interval 0.68-0.98); P = .03], with consistency across estimated glomerular filtration rate categories, urine albumin-to-creatinine ratio levels, and KDIGO risk classification (all P-interaction > .13). Death due to any cause was reduced by 20% [HR 0.80 (0.67-0.95); P = .01], with consistency across estimated glomerular filtration rate categories and KDIGO risk class (P-interaction .21 and .23, respectively). The P-interaction treatment effect for death due to any cause by urine albumin-to-creatinine ratio was .01 [<300 mg/g HR 1.17 (0.83-1.65); ≥300 mg/g HR 0.70 (0.57-0.85)].

conclusionsSemaglutide significantly reduced the risk of CV death/MI/stroke regardless of baseline CKD severity in participants with type 2 diabetes.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Diabetic NephropathiesGlucagon-Like PeptidesHypoglycemic AgentsRenal Insufficiency, ChronicAgedDouble-Blind MethodFemaleGlomerular Filtration RateGlucagon-Like Peptide 1HumansMaleMiddle AgedMyocardial InfarctionSemaglutideGlucagon-Like Peptide 1Glucagon-Like PeptidesHypoglycemic AgentsSemaglutideCardiovascular outcomesChronic kidney diseaseSemaglutideType 2 diabetes

Identifiers

PMID39211948
PMCPMC11931213

What Socratic holds

Texttitle and abstract
LicenceCC BY
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.