Evidence map›Paper›PMID 33608326›Full record

ReviewDiabetes care2021

Metformin Benefits: Another Example for Alternative Energy Substrate Mechanism?

Andrea Giaccari, Anna Solini, Simona Frontoni, Stefano Del Prato

Open access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Diabetes care, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 2 pooled it
3.3field-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.

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

28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 49 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Drug Therapies for Diabetes.International journal of molecular sciences · 2023
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Molecular mechanisms of exercise contributing to tissue regeneration.Signal transduction and targeted therapy · 2022
    Review
  19. Article
  20. Review
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

4 authors at 3 institutions in 1 country.

Andrea GiaccariCenter for Endocrine and Metabolic Diseases, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.ORCID 0000-0002-7462-7792
Anna SoliniDepartment of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy.ORCID 0000-0002-7855-8253
Simona FrontoniUnit of Endocrinology, Diabetes and Metabolism, San Giovanni Calibita Fatebenefratelli Hospital, Rome, Italy.ORCID 0000-0001-8241-7552
Stefano Del PratoSection of Metabolic Diseases and Diabetes, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy stefano.delprato@unipi.it.ORCID 0000-0002-5388-0270
University of Pisa · ITUniversità Cattolica del Sacro Cuore · ITUniversity of Rome Tor Vergata · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Since the UK Prospective Diabetes Study (UKPDS), metformin has been considered the first-line medication for patients with newly diagnosed type 2 diabetes. Though direct evidence from specific trials is still lacking, several studies have suggested that metformin may protect from diabetes- and nondiabetes-related comorbidities, including cardiovascular, renal, neurological, and neoplastic diseases. In the past few decades, several mechanisms of action have been proposed to explain metformin's protective effects, none being final. It is certain, however, that metformin increases lactate production, concentration, and, possibly, oxidation. Once considered a mere waste product of exercising skeletal muscle or anaerobiosis, lactate is now known to act as a major energy shuttle, redistributed from production sites to where it is needed. Through the direct uptake and oxidation of lactate produced elsewhere, all end organs can be rapidly supplied with fundamental energy, skipping glycolysis and its possible byproducts. Increased lactate production (and consequent oxidation) could therefore be considered a positive mechanism of action of metformin, except when, under specific circumstances, metformin and lactate become excessive, increasing the risk of lactic acidosis. We are proposing that, rather than considering metformin-induced lactate production as dangerous, it could be considered a mechanism through which metformin exerts its possible protective effect on the heart, kidneys, and brain and, to some extent, its antineoplastic action.

Indexed as

Acidosis, LacticDiabetes Mellitus, Type 2MetforminHumansHypoglycemic AgentsProspective StudiesHypoglycemic AgentsMetformin

Identifiers

PMID33608326
PMCPMC7896249
OpenAlexW3131218858

What Socratic holds

Texttitle and abstract
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.