Evidence map›Paper›PMID 37438734›Full record

Trial reportCardiovascular diabetology2023

Insulin growth factor axis and cardio-renal risk in diabetic kidney disease: an analysis from the CREDENCE trial.

Reza Mohebi, Yuxi Liu, Michael K Hansen, Yshai Yavin, Naveed Sattar, Carol A Pollock, Javed Butler, Meg Jardine, Serge Masson, Hiddo J L Heerspink and 1 more

Registry-linked trialOpen access · goldFull text readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cardiovascular diabetology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT02065791. Cited by 13 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 2 pooled it
3.4field-weighted citation impact, top 6% 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.

NCT02065791 phase3completed

A Randomized, Double-blind, Event-driven, Placebo-controlled, Multicenter Study of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Subjects With Type 2 Diabetes Mellitus and Diabetic Nephropathy

Ran2014Enrolled4,401Registered outcomes8Posted comparisons8ConditionsDiabetes Mellitus, Type 2, Diabetic NephropathyArmsCanagliflozin, Placebo
Open the trial in the graph
3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. The insulin-like growth factor system and the progression of renal complications of type 2 diabetes.Diabetic medicine : a journal of the British Diabetic Association · 2026
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  6. Article
  7. Review
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  10. Review
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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

11 authors at 10 institutions in 5 countries.

Reza MohebiCardiology Division, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.
Yuxi LiuCardiology Division, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.
Michael K HansenJanssen Research Development, LLC, Spring House, Montgomery, PA, USA.
Yshai YavinJanssen Research Development, LLC, Spring House, Montgomery, PA, USA.
Naveed SattarBHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
Carol A PollockKolling Institute, Royal North Shore Hospital University of Sydney, Sydney, NSW, Australia.
Javed ButlerUniversity of Mississippi Medical Center, Jackson, MS, USA.
Meg JardineThe George Institute for Global Health, UNSW Sydney, Sydney, NSW, Australia.
Serge MassonRoche Diagnostics International, Rotkreuz, Switzerland.
Hiddo J L HeerspinkDepartment Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, The Netherlands.
James L JanuzziCardiology Division, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA. jjanuzzi@partners.org.
Janssen (United States) · USBaim Institute for Clinical Research · USBaylor Scott & White Health · USHarvard University · USMassachusetts General Hospital · USRoche (Switzerland) · CHUniversity of Glasgow · GBUniversity of Groningen · NLUniversity of Sydney · AUUNSW Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe insulin-like growth factors (IGF) play a crucial role in regulating cellular proliferation, apoptosis, and key metabolic pathways. The ratio of IGF-1 to IGF binding protein-3 (IGFBP-3) is an important factor in determining IGF-1 bioactivity. We sought to investigate the association of IGF-1 and IGFBP-3 with cardio-renal outcomes among persons with type 2 diabetes.

methodsSamples were available from 2627 individuals with type 2 diabetes and chronic kidney disease that were randomized to receive canagliflozin or placebo and were followed up for incident cardio-renal events. Primary outcome was defined as a composite of end-stage kidney disease, doubling of the serum creatinine level, or renal/cardiovascular death. IGF-1 and IGFBP-3 were measured at baseline, Year-1 and Year-3. Elevated IGF-1 level was defined according to age-specific cutoffs. Cox proportional hazard regression was used to investigate the association between IGF-1 level, IGFBP-3, and the ratio of IGF-1/IGFBP-3 with clinical outcomes.

resultsElevated IGF-1 was associated with lower glomerular filtration rate at baseline. Treatment with canagliflozin did not significantly change IGF-1 and IGFBP-3 concentrations by 3 years (p-value > 0.05). In multivariable models, elevated IGF-1 (above vs below age-specific cutoffs) was associated with the primary composite outcome (incidence rate:17.8% vs. 12.7% with a hazard ratio [HR]: 1.52; 95% confidence interval CI 1.09-2.13;P: 0.01), renal composite outcome (HR: 1.65; 95% CI 1.14-2.41; P: 0.01), and all-cause mortality (HR: 1.52; 95% CI 1.00-2.32; P; 0.05). Elevations in log IGFBP-3 did not associate with any clinical outcomes. Increase in log IGF-1/IGFBP-3 ratio was also associated with a higher risk of the primary composite outcome (HR per unit increase: 1.57; 95% CI 1.09-2.26; P; 0.01).

conclusionsThese results further suggest potential importance of IGF biology in the risk for cardio-renal outcomes in type 2 diabetes. SGLT2 inhibition has no impact on the biology of IGF despite its significant influence on outcomes.

trial registrationCREDENCE; ClinicalTrials.gov Identifier: NCT02065791.

Indexed as

Diabetes Mellitus, Type 2Diabetic NephropathiesCanagliflozinHumansInsulinInsulin-Like Growth Factor Binding Protein 3Insulin-Like Growth Factor ICanagliflozinInsulinInsulin-Like Growth Factor Binding Protein 3Insulin-Like Growth Factor ICanagliflozinChronic kidney diseaseDiabetes mellitusIGF-1

Identifiers

PMID37438734
PMCPMC10339517
OpenAlexW4384071484

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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.