Evidence mapPaperPMID 35787704Full record

Trial reportCardiovascular diabetology2022

Liver function markers predict cardiovascular and renal outcomes in the CANVAS Program.

Giulia Ferrannini, Norman Rosenthal, Michael K Hansen, Ele Ferrannini

Open access · goldFull text readClinical Trial
In one paragraph

Trial report in Cardiovascular diabetology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

3 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
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

4 authors at 4 institutions in 3 countries.

Giulia FerranniniDepartment of Medicine Solna, Karolinska Institutet, Norrbacka, S1:02, 171 76, Stockholm, Sweden. giulia.ferrannini@ki.se.
Norman RosenthalJanssen Research & Development, LLC, 920 US-202, Raritan, NJ, 08869, USA.
Michael K HansenJanssen Research & Development, LLC, Welsh & McKean Rds., Spring House, PA, 19477, USA.
Ele FerranniniCNR Institute of Clinical Physiology, Via Savi 12, 56126, Pisa, Italy.
Istituto di Fisiologia Clinica · ITJanssen (United States) · USKarolinska Institutet · SESpringhouse · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRaised liver function tests (LFTs) have been correlated with multiple metabolic abnormalities and variably associated with cardiorenal outcomes. We sought to systematically test the relationship between LFT levels within the accepted range and major cardiorenal outcomes in a large clinical trial in type 2 diabetes, and the possible impact of placebo-controlled canagliflozin treatment.

methodsWe measured serum alanine aminotransferase (ALT), aspartic aminotransferase (AST), gamma-glutamyl transferase (γGT), alkaline phosphatase (ALP), and bilirubin concentrations in 10,142 patients, at baseline and repeatedly over follow-up. The relation of LFTs to first hospitalized heart failure (HHF), cardiovascular (CV) and all-cause mortality, and progression of renal impairment was investigated using multivariate proportional-hazards models.

resultsIn univariate association, ALT was reciprocally predictive, and ALP was positively predictive, of all adjudicated outcomes; γGT also was directly associated with CV-but not renal-outcomes. In multivariate models including all 5 LFTs and 19 potential clinical confounders, ALT was independently associated with lower, and γGT with higher, CV outcomes risk. Canagliflozin treatment significantly reduced ALT, AST, and γGT over time. In a fully adjusted model including updated LFT levels and treatment, γGT was independently associated with CV and all-cause mortality, ALP with renal dysfunction progression, and canagliflozin treatment with significant reduction in HHF and renal risk.

conclusionsHigher γGT levels are top LFT markers of risk of HHF and death in patients with diabetes and high CV risk, while ALT are protective. Canagliflozin lowers the risk of HHF and renal damage independently of LFTs and potential confounders.

Indexed as

CanagliflozinDiabetes Mellitus, Type 2Heart FailureLiver Function TestsSodium-Glucose Transporter 2 InhibitorsAlkaline PhosphataseBiomarkersHumansLiverAlkaline PhosphataseBiomarkersCanagliflozinSodium-Glucose Transporter 2 InhibitorsAlanine aminotransferaseHeart failureLiverRenal morbiditySGLT2 inhibitor

Identifiers

PMID35787704
PMCPMC9254689
OpenAlexW4283797559

What Socratic holds

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Registered trials

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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.