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Metformin Benefits: Another Example for Alternative Energy Substrate Mechanism?

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 nondi...

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Autores principales: Giaccari, Andrea, Solini, Anna, Frontoni, Simona, Del Prato, Stefano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896249/
https://www.ncbi.nlm.nih.gov/pubmed/33608326
http://dx.doi.org/10.2337/dc20-1964
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author Giaccari, Andrea
Solini, Anna
Frontoni, Simona
Del Prato, Stefano
author_facet Giaccari, Andrea
Solini, Anna
Frontoni, Simona
Del Prato, Stefano
author_sort Giaccari, Andrea
collection PubMed
description 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.
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spelling pubmed-78962492021-02-22 Metformin Benefits: Another Example for Alternative Energy Substrate Mechanism? Giaccari, Andrea Solini, Anna Frontoni, Simona Del Prato, Stefano Diabetes Care Perspectives in Care 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. American Diabetes Association 2021-03 2021-02-11 /pmc/articles/PMC7896249/ /pubmed/33608326 http://dx.doi.org/10.2337/dc20-1964 Text en © 2021 by the American Diabetes Association https://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license.
spellingShingle Perspectives in Care
Giaccari, Andrea
Solini, Anna
Frontoni, Simona
Del Prato, Stefano
Metformin Benefits: Another Example for Alternative Energy Substrate Mechanism?
title Metformin Benefits: Another Example for Alternative Energy Substrate Mechanism?
title_full Metformin Benefits: Another Example for Alternative Energy Substrate Mechanism?
title_fullStr Metformin Benefits: Another Example for Alternative Energy Substrate Mechanism?
title_full_unstemmed Metformin Benefits: Another Example for Alternative Energy Substrate Mechanism?
title_short Metformin Benefits: Another Example for Alternative Energy Substrate Mechanism?
title_sort metformin benefits: another example for alternative energy substrate mechanism?
topic Perspectives in Care
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896249/
https://www.ncbi.nlm.nih.gov/pubmed/33608326
http://dx.doi.org/10.2337/dc20-1964
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