Trial reportJCI insight2024

Fasting substrates predict chronic kidney disease progression in CREDENCE trial patients with type 2 diabetes.

Ele Ferrannini, Simona Baldi, Maria Tiziana Scozzaro, Giulia Ferrannini, Michael K Hansen

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in JCI insight, 2024. The graph read 4 numbers from its abstract, feeding 1 cell of the map: it supports the treatment in 1. Not yet cited in PubMed.

4numbers the graph read from it
1cell of the map it votes in
0citing 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.

← favours the treatmentfavours the comparator →
0.51 · no effect
Cardiovascular eventsfavours the treatment · against placebo · t2d, ckdfeeds one cell of the map
HR 0.670.48 to 0.95
We tested whether the circulating substrate mix is related to CKD progression and cardiovascular outcomes in patients with type 2 diabetes (T2D) and albuminuric CKD in the CREDENCE trial.METHODSWe measured fasting substrates in 2,543 plasma samples at baseline and 1 year after randomization to either 100 mg canagliflozin or placebo and used multivariate Cox models to explore their association with CKD progression, heart failure hospitalization/cardiovascular death (hHF/CVD), and mortality.RESULTSHigher baseline lactate and free fatty acids (FFAs) were independently associated with a lower risk of CKD progression (HR = 0.73 [95% CI: 0.54-0.98] and HR = 0.67 [95% CI: 0.48-0.95], respectively) and hHF/CVD HR = 0.70 [95% CI: 0.50-0.99] and HR = 0.63 [95% CI: 0.42-0.94]).
Cardiovascular eventsfavours the treatment · against placebo · t2d, ckdfeeds one cell of the map
HR 0.730.54 to 0.98
We tested whether the circulating substrate mix is related to CKD progression and cardiovascular outcomes in patients with type 2 diabetes (T2D) and albuminuric CKD in the CREDENCE trial.METHODSWe measured fasting substrates in 2,543 plasma samples at baseline and 1 year after randomization to either 100 mg canagliflozin or placebo and used multivariate Cox models to explore their association with CKD progression, heart failure hospitalization/cardiovascular death (hHF/CVD), and mortality.RESULTSHigher baseline lactate and free fatty acids (FFAs) were independently associated with a lower risk of CKD progression (HR = 0.73 [95% CI: 0.54-0.98] and HR = 0.67 [95% CI: 0.48-0.95], respectively) and hHF/CVD HR = 0.70 [95% CI: 0.50-0.99] and HR = 0.63 [95% CI: 0.42-0.94]).
Cardiovascular eventsfavours the treatment · against placebo · t2d, ckdfeeds one cell of the map
HR 0.700.50 to 0.99
We tested whether the circulating substrate mix is related to CKD progression and cardiovascular outcomes in patients with type 2 diabetes (T2D) and albuminuric CKD in the CREDENCE trial.METHODSWe measured fasting substrates in 2,543 plasma samples at baseline and 1 year after randomization to either 100 mg canagliflozin or placebo and used multivariate Cox models to explore their association with CKD progression, heart failure hospitalization/cardiovascular death (hHF/CVD), and mortality.RESULTSHigher baseline lactate and free fatty acids (FFAs) were independently associated with a lower risk of CKD progression (HR = 0.73 [95% CI: 0.54-0.98] and HR = 0.67 [95% CI: 0.48-0.95], respectively) and hHF/CVD HR = 0.70 [95% CI: 0.50-0.99] and HR = 0.63 [95% CI: 0.42-0.94]).
Cardiovascular eventsfavours the treatment · against placebo · t2d, ckdfeeds one cell of the map
HR 0.630.42 to 0.94
We tested whether the circulating substrate mix is related to CKD progression and cardiovascular outcomes in patients with type 2 diabetes (T2D) and albuminuric CKD in the CREDENCE trial.METHODSWe measured fasting substrates in 2,543 plasma samples at baseline and 1 year after randomization to either 100 mg canagliflozin or placebo and used multivariate Cox models to explore their association with CKD progression, heart failure hospitalization/cardiovascular death (hHF/CVD), and mortality.RESULTSHigher baseline lactate and free fatty acids (FFAs) were independently associated with a lower risk of CKD progression (HR = 0.73 [95% CI: 0.54-0.98] and HR = 0.67 [95% CI: 0.48-0.95], respectively) and hHF/CVD HR = 0.70 [95% CI: 0.50-0.99] and HR = 0.63 [95% CI: 0.42-0.94]).

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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.

Diet, exercise & lifestyle×cardiovascular events

SupportsOpen on the map →What to test next →

2 readable studies in this cell: 2 favour the treatment, 0 find no difference, 0 favour the comparator.

Belief with this paper
0.50one trial · 1 family supports, 0 contradict · against placebo
Without it
0.25This paper moves it by +0.25. It would be no deciding trial.
← favours the treatmentfavours the comparator →
1 · no effect
This paper · 2024
HR 0.670.48 to 0.95
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

5 authors.

Ele FerranniniCNR (National Research Council) Institute of Clinical Physiology, Pisa, Italy.
Simona BaldiDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Maria Tiziana ScozzaroDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Giulia FerranniniDepartment of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Michael K HansenJanssen Research & Development, LLC, Raritan, New Jersey, USA.

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

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

BACKGROUNDSodium-glucose cotransporter 2 inhibitors slow down progression of chronic kidney disease (CKD). We tested whether the circulating substrate mix is related to CKD progression and cardiovascular outcomes in patients with type 2 diabetes (T2D) and albuminuric CKD in the CREDENCE trial.METHODSWe measured fasting substrates in 2,543 plasma samples at baseline and 1 year after randomization to either 100 mg canagliflozin or placebo and used multivariate Cox models to explore their association with CKD progression, heart failure hospitalization/cardiovascular death (hHF/CVD), and mortality.RESULTSHigher baseline lactate and free fatty acids (FFAs) were independently associated with a lower risk of CKD progression (HR = 0.73 [95% CI: 0.54-0.98] and HR = 0.67 [95% CI: 0.48-0.95], respectively) and hHF/CVD HR = 0.70 [95% CI: 0.50-0.99] and HR = 0.63 [95% CI: 0.42-0.94]). Canagliflozin led to a rise in plasma FFAs, glycerol, β-hydroxybutyrate, and acetoacetate. Changes in substrate between baseline and year 1 predicted an approximately 30% reduction in relative risk of both CKD progression and hHF/CVD independently of treatment. More patients who did not respond to canagliflozin treatment in terms of CKD progression belonged to the bottom lactate and FFA distribution tertiles.CONCLUSIONIn T2D patients with albuminuric CKD, basic energy substrates selectively influenced major long-term endpoints; canagliflozin treatment amplified their effects by chronically raising their circulating levels.

Indexed as

CanagliflozinDiabetes Mellitus, Type 2Disease ProgressionRenal Insufficiency, ChronicSodium-Glucose Transporter 2 Inhibitors3-Hydroxybutyric AcidAgedDiabetic NephropathiesFastingFatty Acids, NonesterifiedFemaleGlycerolHumansLactic AcidMaleMiddle Aged3-Hydroxybutyric AcidCanagliflozinFatty Acids, NonesterifiedGlycerolLactic AcidSodium-Glucose Transporter 2 InhibitorsCardiologyDiabetesDrug therapyEndocrinologyIntermediary metabolism

Identifiers

PMID39704168
PMCPMC11665565

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.