Evidence map›Paper›PMID 24393785›Full record

ReviewNature reviews. Endocrinology2014

Metformin--mode of action and clinical implications for diabetes and cancer.

Ida Pernicova, Márta Korbonits

Registry-linked trialAbstract readReview
PubMed Publisher
In one paragraph

Review in Nature reviews. Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03772964 (A Pilot Study), which is not on this map. Cited by 696 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
696citing papers in PubMed, 9 pooled it
45.7field-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.

NCT03772964 phase1 / phase2completednot on this mapstarted 2019, after this paper: background citation

A Pilot Study: Metformin as an Inflammatory Modulating Therapy in Older Adults Without Diabetes

TypeinterventionalSponsorBrian ZuckerbraunRan2019 to 2020Enrolled32ConditionsInflammatory ResponseArmsMetFORMIN Hydrochloride ER, Placebo
3 · Its place in the literature

Who cites it

696 citing papers in PubMed, 9 syntheses or guidelines pooled it, 1,353 citations in OpenAlex.

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  15. Genetic discovery using deep learning-derived optic nerve integrity phenotypes.medRxiv : the preprint server for health sciences · 2026
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636 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

2 authors at 1 institution in 1 country.

Ida PernicovaDepartment of Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1A 6BQ, UK.
Márta KorbonitsDepartment of Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1A 6BQ, UK.
William Harvey Research Institute · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metformin has been the mainstay of therapy for diabetes mellitus for many years; however, the mechanistic aspects of metformin action remained ill-defined. Recent advances revealed that this drug, in addition to its glucose-lowering action, might be promising for specifically targeting metabolic differences between normal and abnormal metabolic signalling. The knowledge gained from dissecting the principal mechanisms by which metformin works can help us to develop novel treatments. The centre of metformin's mechanism of action is the alteration of the energy metabolism of the cell. Metformin exerts its prevailing, glucose-lowering effect by inhibiting hepatic gluconeogenesis and opposing the action of glucagon. The inhibition of mitochondrial complex I results in defective cAMP and protein kinase A signalling in response to glucagon. Stimulation of 5'-AMP-activated protein kinase, although dispensable for the glucose-lowering effect of metformin, confers insulin sensitivity, mainly by modulating lipid metabolism. Metformin might influence tumourigenesis, both indirectly, through the systemic reduction of insulin levels, and directly, via the induction of energetic stress; however, these effects require further investigation. Here, we discuss the updated understanding of the antigluconeogenic action of metformin in the liver and the implications of the discoveries of metformin targets for the treatment of diabetes mellitus and cancer.

Indexed as

AMP-Activated Protein KinasesDiabetes Mellitus, Type 2Energy MetabolismGlucagonGluconeogenesisHumansLiverMetforminSignal TransductionAMP-Activated Protein KinasesGlucagonMetformin

Identifiers

PMID24393785
OpenAlexW2148755064

What OpenQuestion holds

Texttitle and abstract
Read underepoch 390

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.