Evidence map›Paper›PMID 40952180›Full record

Trial reportESC heart failure2025

Galectin-3 and kidney function in type 2 diabetes treated with dapagliflozin: Analysis from DECLARE-TIMI 58.

Paul M Haller, Stephen D Wiviott, David D Berg, Petr Jarolim, Erica L Goodrich, Deepak L Bhatt, Ingrid Gause-Nilsson, Lawrence A Leiter, Darren K McGuire, John P H Wilding and 3 more

Registry-linked trialAbstract readRandomized Controlled TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in ESC heart failure, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT01730534. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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.

NCT01730534 phase3completed

Dapagliflozin Effect on Cardiovascular Events A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Effect of Dapagliflozin 10 mg Once Daily on the Incidence of Cardiovascular Death, Myocardial Infarction or Ischemic Stroke in Patients With Type 2 Diabetes

Ran2013Enrolled17,190Registered outcomes4Posted comparisons4ConditionsDiabetes Mellitus, Non-Insulin-Dependent, High Risk for Cardiovascular EventArmsDapagliflozin 10 mg, Placebo tablet
Open the trial in the graph
3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Trial
  2. Review
  3. Article
  4. Article
  5. Review
  6. 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

13 authors.

Paul M HallerTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.ORCID https://orcid.org/0000-0002-7714-4446
Stephen D WiviottTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
David D BergTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Petr JarolimDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Erica L GoodrichTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Deepak L BhattMount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Ingrid Gause-NilssonBioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Lawrence A LeiterLi Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Canada.
Darren K McGuireDivision of Cardiology, University of Texas Southwestern Medical Center, and Parkland Health System, Dallas, Texas, USA.
John P H WildingInstitute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
Itamar RazDiabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Marc S SabatineTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
David A MorrowTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Funding

Abbott LaboratoriesAstraZenecaDeutsche Forschungsgemeinschaft 10086/1-1
6 · The paper itself

Abstract

backgroundGalectin-3 (Gal-3) is a circulating biomarker of fibrosis, with higher levels being associated with an increased risk of progression of heart failure and kidney disease. Patients with type 2 diabetes mellitus (T2DM) are at increased risk of both.

methodsDECLARE-TIMI 58 was a randomized, placebo-controlled trial of dapagliflozin in patients with T2DM with or at high risk for atherosclerotic cardiovascular disease and creatinine clearance ≥60 mL/min. In a nested biomarker substudy, Gal-3 was measured at baseline and in adjusted analyses associated with the prespecified kidney-specific composite endpoint [Kidney-EP; sustained ≥40% decrease in estimated glomerular filtration rate (eGFR) to <60 mL/min, new end-stage kidney disease or adjudicated kidney-related death].

resultsAmong 14 530 pts, median Gal-3 was 14.9 ng/mL [interquartile range (IQR), 11.9, 18.4]. Gal-3 was weakly associated with urine albumin creatinine ratio (r = 0.098, P < 0.0001) and eGFR (r = -0.27, P < 0.001) at baseline and independently associated with the Kidney-EP:adj hazard ratio (HR) 1.15 [95% confidence interval (CI) 1.03, 1.28] per 1-SD log (Gal-3), P = 0.013. Dapagliflozin significantly reduced the relative risk of the Kidney-EP across quartiles of baseline Gal-3 [overall HR 0.45 (95% CI 0.23, 0.85), P < 0.0001; P interaction = 0.87]. A greater risk difference was observed with dapagliflozin in patients with higher Gal-3, in whom a higher absolute risk at baseline was observed [absolute risk reduction (ARR) Q4 1.9 (95% CI 0.6, 3.2) vs. Q1 0.6% (-0.1, 1.3), ARR P trend 0.048].

conclusionsPlasma Gal-3 is independently associated with the progression of kidney dysfunction in patients with T2DM and normal kidney function. There was a gradient of greater absolute benefit for reducing kidney disease progression in patients treated with dapagliflozin and with higher Gal-3 concentrations at baseline, in whom a higher absolute risk was observed. REGISTRATION: clinicaltrials.gov (NCT01730534).

Indexed as

Benzhydryl CompoundsDiabetes Mellitus, Type 2Diabetic NephropathiesGalectin 3Glomerular Filtration RateGlucosidesKidneyAgedBiomarkersBlood ProteinsDisease ProgressionDouble-Blind MethodFemaleFollow-Up StudiesGalectinsHumansBenzhydryl CompoundsBiomarkersBlood ProteinsdapagliflozinGalectin 3GalectinsGlucosidesLGALS3 protein, humanSodium-Glucose Transporter 2 Inhibitorsdapagliflozingalectin‐3kidney diseaserenal functionsglt2‐inhibitortype 2 diabetes

Identifiers

PMID40952180
PMCPMC12719846

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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.