Evidence mapPaperPMID 34208371Full record

ReviewInternational journal of molecular sciences2021

The Hormetic Effect of Metformin: "Less Is More"?

Isabella Panfoli, Alessandra Puddu, Nadia Bertola, Silvia Ravera, Davide Maggi

Open access · goldAbstract readReview
In one paragraph

Review in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

19 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Antidiabetic Effects and Mechanisms of Action of Uncaria gambir Roxb. in Diabetic Sprague-Dawley Rats.Journal of the American Association for Laboratory Animal Science : JAALAS · 2025
    Article
  7. Article
  8. Ethnopharmacological Study ofPlants (Basel, Switzerland) · 2024
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Advances in research on pharmacotherapy of sarcopenia.Aging medicine (Milton (N.S.W)) · 2021
    Review
  18. Review
  19. Article
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

5 authors at 1 institution in 1 country.

Isabella PanfoliBiochemistry Lab., Department of Pharmacy, University of Genoa, Viale Benedetto XV, 3, 16132 Genoa, Italy.ORCID 0000-0002-6261-1128
Alessandra PudduDepartment of Internal Medicine and Medical Specialties, University of Genoa, Viale Benedetto XV, 6, 16132 Genoa, Italy.ORCID 0000-0002-9084-2636
Nadia BertolaDepartment of Experimental Medicine, University of Genoa, Via De Toni, 14, 16132 Genoa, Italy.ORCID 0000-0003-4591-3260
Silvia RaveraDepartment of Experimental Medicine, University of Genoa, Via De Toni, 14, 16132 Genoa, Italy.ORCID 0000-0002-0803-1042
Davide MaggiDepartment of Internal Medicine and Medical Specialties, University of Genoa, Viale Benedetto XV, 6, 16132 Genoa, Italy.ORCID 0000-0003-3928-1295
University of Genoa · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metformin (MTF) is the first-line therapy for type 2 diabetes (T2DM). The euglycemic effect of MTF is due to the inhibition of hepatic glucose production. Literature reports that the principal molecular mechanism of MTF is the activation of 5'-AMP-activated protein kinase (AMPK) due to the decrement of ATP intracellular content consequent to the inhibition of Complex I, although this effect is obtained only at millimolar concentrations. Conversely, micromolar MTF seems to activate the mitochondrial electron transport chain, increasing ATP production and limiting oxidative stress. This evidence sustains the idea that MTF exerts a hormetic effect based on its concentration in the target tissue. Therefore, in this review we describe the effects of MTF on T2DM on the principal target organs, such as liver, gut, adipose tissue, endothelium, heart, and skeletal muscle. In particular, data indicate that all organs, except the gut, accumulate MTF in the micromolar range when administered in therapeutic doses, unmasking molecular mechanisms that do not depend on Complex I inhibition.

Indexed as

AnimalsHormesisHumansMetforminModels, BiologicalOrgan SpecificityMetforminadipose tissuediabetesendotheliumguthearthormetic effectliverMTFskeletal muscle

Identifiers

PMID34208371
PMCPMC8231127
OpenAlexW3167479230

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.