Trial reportCardiovascular diabetology2022

Association between serum insulin levels and heart failure-related parameters in patients with type 2 diabetes and heart failure treated with canagliflozin: a post-hoc analysis of the randomized CANDLE trial.

Atsushi Tanaka, Takumi Imai, Michio Shimabukuro, Isao Taguchi, Akira Sezai, Shigeru Toyoda, Hirotaka Watada, Junya Ako, Koichi Node, CANDLE trial investigators

Open access · goldFull text readMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Cardiovascular diabetology, 2022. The graph read 1 number from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. Cited by 1 paper.

1number the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.4field-weighted citation impact, top 36% 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.

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

Glycemic controldirection of benefit for this outcome is not defined · head-to-head · t2d, heart_failurefeeds 2 cells of the map
reduced -24.0p < 0.001
Canagliflozin treatment significantly reduced insulin concentrations at week 24 (p < 0.001), and the between-group difference (canagliflozin minus glimepiride) in those changes was - 3.52 mU/L (95% confidence interval, - 4.85 to - 2.19; p < 0.001).

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.

Insulin×glycemic control

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

40 readable studies in this cell: 15 favour the treatment, 14 find no difference, 14 favour the comparator.

Belief with this paper
0.50contested · 9 families support, 6 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
NCT036893742,274 enrolled · 2018
Δ -0.29-0.38 to -0.20
NCT037306622,002 enrolled · 2018
Δ -0.99-1.13 to -0.86
NCT013360231,663 enrolled · 2011
Treatment contrast -0.64-0.75 to -0.53
NCT038829701,444 enrolled · 2019
Δ -0.86-1.00 to -0.72
NCT045379231,428 enrolled · 2020
Δ -1.10-1.24 to -0.97
NCT032680051,264 enrolled · 2017
Δ -0.04-0.11 to 0.03
NCT020581471,170 enrolled · 2014
Δ -0.78-0.90 to -0.67
NCT021289321,089 enrolled · 2014
Δ -0.81-0.96 to -0.67
NCT009606611,036 enrolled · 2009
Δ -0.04-0.18 to 0.11
NCT00856986987 enrolled · 2009
Δ -0.52-0.68 to -0.36
NCT01117350978 enrolled · 2010
Δ 2.54-3.88 to 8.93
NCT03214380933 enrolled · 2017
Δ 0.06-0.05 to 0.16

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

SGLT2 inhibitors×glycemic control

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

40 readable studies in this cell: 81 favour the treatment, 11 find no difference, 4 favour the comparator.

Belief with this paper
0.92replicated · 70 families support, 6 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT010326294,330 enrolled · 2009
Δ 2.79-1.57 to 7.15
NCT011374742,996 enrolled · 2010
Δ -0.46-0.59 to -0.33
NCT011956622,245 enrolled · 2010
Δ -0.61-0.76 to -0.46
NCT010956661,484 enrolled · 2010
Δ -0.59-0.76 to -0.42
NCT009688121,452 enrolled · 2009
Δ -0.01-0.11 to 0.09
NCT017190031,413 enrolled · 2012
Adjusted mean -0.33-0.56 to -0.10
NCT011066771,284 enrolled · 2010
Δ -0.62-0.76 to -0.48
NCT016060071,282 enrolled · 2012
Δ -0.59-0.81 to -0.37
NCT006732311,240 enrolled · 2008
Δ -0.45-0.59 to -0.31
NCT020991101,233 enrolled · 2014
Δ -0.43-0.60 to -0.27
NCT006609071,217 enrolled · 2008
Δ 0.00-0.11 to 0.11
NCT018093271,186 enrolled · 2013
Δ -0.46-0.66 to -0.27

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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. Article
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

10 authors at 8 institutions in 1 country.

Atsushi TanakaDepartment of Cardiovascular Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan. tanakaa2@cc.saga-u.ac.jp.
Takumi ImaiDepartment of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
Michio ShimabukuroDepartment of Diabetes, Endocrinology, and Metabolism, Fukushima Medical University, Fukushima, Japan.
Isao TaguchiDepartment of Cardiology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan.
Akira SezaiDepartment of Cardiovascular Surgery, Nihon University School of Medicine, Tokyo, Japan.
Shigeru ToyodaDepartment of Cardiovascular Medicine, Dokkyo Medical University School of Medicine, Mibu, Japan.
Hirotaka WatadaDepartment of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Junya AkoDepartment of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
Koichi NodeDepartment of Cardiovascular Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan. node@cc.saga-u.ac.jp.
CANDLE trial investigators
Saga University · JPDokkyo Medical University · JPFukushima Medical University · JPJuntendo University · JPKitasato University · JPNihon University · JPOsaka Metropolitan UniversitySocial Insurance Saitama Chuo Hospital · JP

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.

backgroundInsulin resistance and hyperinsulinemia in patients with type 2 diabetes (T2D) are adversely associated with the development and worsening of heart failure (HF). Herein, we sought to investigate the effect of canagliflozin on insulin concentrations and the associations of changes in insulin concentrations with HF-related clinical parameters in patients with T2D and HF.

methodsThis was a post-hoc analysis of the investigator-initiated, multicenter, open-label, randomized, controlled CANDLE trial for patients with T2D and chronic HF (UMIN000017669). The endpoints were the effects of 24 weeks of canagliflozin treatment, relative to glimepiride treatment, on insulin concentrations and the relationship between changes in insulin concentrations and clinical parameters of interest, including New York Heart Association (NYHA) classification. The effects of canagliflozin on those parameters were also analyzed by baseline insulin level.

resultsAmong the participants in the CANDLE trial, a total of 129 patients (canagliflozin, n = 64; glimepiride, n = 65) who were non-insulin users with available serum insulin data both at baseline and week 24 were included in this analysis. Overall, the mean age was 69.0 ± 9.4 years; 75% were male; the mean HbA1c was 6.8 ± 0.7%; and the mean left ventricular ejection fraction was 59.0 ± 14.1%, with parameters roughly balanced between treatment groups. Canagliflozin treatment significantly reduced insulin concentrations at week 24 (p < 0.001), and the between-group difference (canagliflozin minus glimepiride) in those changes was - 3.52 mU/L (95% confidence interval, - 4.85 to - 2.19; p < 0.001). Decreases in insulin concentrations, irrespective of baseline insulin level, were significantly associated with improvement in NYHA class in patients treated with canagliflozin.

conclusionOur findings suggest that canagliflozin treatment in patients with T2D and HF ameliorated excess insulin overload, contributing to the improvement of clinical HF status.

trial registrationUniversity Medical Information Network Clinical Trial Registry, number 000017669, Registered on May 25, 2015.

Indexed as

Diabetes Mellitus, Type 2Heart FailureAgedBlood GlucoseCanagliflozinFemaleHumansInsulinMaleMiddle AgedStroke VolumeTreatment OutcomeVentricular Function, LeftBlood GlucoseCanagliflozinInsulinCanagliflozinChronic heart failureGlimepirideInsulinType 2 diabetes

Identifiers

PMID35941584
PMCPMC9358857
OpenAlexW4290652886

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.