Evidence mapPaperPMID 23715754Full record

Trial reportDiabetes care2013

Dual peroxisome proliferator-activated receptor α/δ agonist GFT505 improves hepatic and peripheral insulin sensitivity in abdominally obese subjects.

Bertrand Cariou, Rémy Hanf, Stéphanie Lambert-Porcheron, Yassine Zaïr, Valérie Sauvinet, Benoit Noël, Laurent Flet, Hubert Vidal, Bart Staels, Martine Laville

Open access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetes care, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed, 1 pooled it
20.9field-weighted citation impact, top 1% 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

96 citing papers in PubMed, 1 synthesis or guideline pooled it, 206 citations in OpenAlex.

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  18. Review article: vascular effects of PPARs in the context of NASH.Alimentary pharmacology & therapeutics · 2022
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36 more citing papers are in PubMed but not listed here.

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

10 authors at 6 institutions in 1 country.

Bertrand CariouCorresponding author: Bertrand Cariou, bertrand.cariou@univ-nantes.fr.
Rémy Hanf
Stéphanie Lambert-Porcheron
Yassine Zaïr
Valérie Sauvinet
Benoit Noël
Laurent Flet
Hubert Vidal
Bart Staels
Martine Laville
Centre Hospitalier Universitaire de Nantes · FRCentre de Recherche en Nutrition Humaine Rhône-Alpes · FRGenfit (France) · FRHospices Civils de Lyon · FRUniversité Claude Bernard Lyon 1 · FRUniversité Lille Nord de France · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThe development of new insulin sensitizers is an unmet need for the treatment of type 2 diabetes. We investigated the effect of GFT505, a dual peroxisome proliferator-activated receptor (PPAR)-α/δ agonist, on peripheral and hepatic insulin sensitivity. RESEARCH DESIGN AND

methodsTwenty-two abdominally obese insulin-resistant males (homeostasis model assessment of insulin resistance>3) were randomly assigned in a randomized crossover study to subsequent 8-week treatment periods with GFT505 (80 mg/day) or placebo, followed by a two-step hyperinsulinemic-euglycemic insulin clamp with a glucose tracer to calculate endogenous glucose production (EGP). The primary end point was the improvement in glucose infusion rate (GIR). Gene expression analysis was performed on skeletal muscle biopsy specimens.

resultsGFT505 improved peripheral insulin sensitivity, with a 21% (P=0.048) increase of the GIR at the second insulin infusion period. GFT505 also enhanced hepatic insulin sensitivity, with a 44% (P=0.006) increase of insulin suppression of EGP at the first insulin infusion period. Insulin-suppressed plasma free fatty acid concentrations were significantly reduced on GFT505 treatment (0.21±0.07 vs. 0.27±0.11 mmol/L; P=0.006). Neither PPARα nor PPARδ target genes were induced in skeletal muscle, suggesting a liver-targeted action of GFT505. GFT505 significantly reduced fasting plasma triglycerides (-21%; P=0.003) and LDL cholesterol (-13%; P=0.0006), as well as liver enzyme concentrations (γ-glutamyltranspeptidase: -30.4%, P=0.003; alanine aminotransferase: -20.5%, P=0.004). There was no safety concern or any indication of PPARγ activation with GFT505.

conclusionsThe dual PPARα/δ agonist GFT505 is a liver-targeted insulin-sensitizer that is a promising drug candidate for the treatment of type 2 diabetes and nonalcoholic fatty liver disease.

Indexed as

AdultChalconesCross-Over StudiesFemaleHumansInsulin ResistanceLipoproteinsLiverMaleMiddle AgedMuscle, SkeletalObesityPPAR alphaPPAR deltaPropionates2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acidChalconesLipoproteinsPPAR alphaPPAR deltaPropionates

Identifiers

PMID23715754
PMCPMC3781493
OpenAlexW2066841620

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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.