Evidence mapPaperPMID 32780768Full record

ArticlePloS one2020

Whole-blood transcriptome profiling reveals signatures of metformin and its therapeutic response.

Monta Briviba, Laura Ansone, Ivars Silamikelis, Vita Rovite, Ilze Elbere, Laila Silamikele, Ineta Kalnina, Davids Fridmanis, Jelizaveta Sokolovska, Ilze Konrade and 2 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

13 citing papers in PubMed, 26 citations in OpenAlex.

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  8. Recent Multiomics Approaches in Endometrial Cancer.International journal of molecular sciences · 2022
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  10. Commentary: Novel strategies and new tools to curtail the health effects of pesticides.Environmental health : a global access science source · 2021
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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

12 authors at 2 institutions in 1 country.

Monta BrivibaLatvian Biomedical Research and Study Centre, Riga, Latvia.
Laura AnsoneLatvian Biomedical Research and Study Centre, Riga, Latvia.
Ivars SilamikelisLatvian Biomedical Research and Study Centre, Riga, Latvia.
Vita RoviteLatvian Biomedical Research and Study Centre, Riga, Latvia.
Ilze ElbereLatvian Biomedical Research and Study Centre, Riga, Latvia.
Laila SilamikeleLatvian Biomedical Research and Study Centre, Riga, Latvia.
Ineta KalninaLatvian Biomedical Research and Study Centre, Riga, Latvia.
Davids FridmanisLatvian Biomedical Research and Study Centre, Riga, Latvia.
Jelizaveta SokolovskaFaculty of Medicine, University of Latvia, Riga, Latvia.
Ilze KonradeLatvian Biomedical Research and Study Centre, Riga, Latvia.
Valdis PiragsLatvian Biomedical Research and Study Centre, Riga, Latvia.
Janis KlovinsLatvian Biomedical Research and Study Centre, Riga, Latvia.ORCID 0000-0001-8362-5505
Latvian Biomedical Research and Study Centre · LVUniversity of Latvia · LV

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metformin, a biguanide agent, is the first-line treatment for type 2 diabetes mellitus due to its glucose-lowering effect. Despite its wide application in the treatment of multiple health conditions, the glycemic response to metformin is highly variable, emphasizing the need for reliable biomarkers. We chose the RNA-Seq-based comparative transcriptomics approach to evaluate the systemic effect of metformin and highlight potential predictive biomarkers of metformin response in drug-naïve volunteers with type 2 diabetes in vivo. The longitudinal blood-derived transcriptome analysis revealed metformin-induced differential expression of novel and previously described genes involved in cholesterol homeostasis (SLC46A1 and LRP1), cancer development (CYP1B1, STAB1, CCR2, TMEM176B), and immune responses (CD14, CD163) after administration of metformin for three months. We demonstrate for the first time a transcriptome-based molecular discrimination between metformin responders (delta HbA1c ≥ 1% or 12.6 mmol/mol) and non-responders (delta HbA1c < 1% or 12.6 mmol/mol), that is determined by expression levels of 56 genes, explaining 13.9% of the variance in the therapeutic efficacy of the drug. Moreover, we found a significant upregulation of IRS2 gene (log2FC 0.89) in responders compared to non-responders before the use of metformin. Finally, we provide evidence for the mitochondrial respiratory complex I as one of the factors related to the high variability of the therapeutic response to metformin in patients with type 2 diabetes mellitus.

Indexed as

Blood Chemical AnalysisGene Expression ProfilingAgedCholesterolFemaleHomeostasisHumansMaleMetforminMiddle AgedCholesterolMetformin

Identifiers

PMID32780768
PMCPMC7418999
OpenAlexW3048445428

What Socratic holds

Textmetadata
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.