Metformin Action: Concentrations Matter

He, Ling; Wondisford, Fredric E.

doi:10.1016/j.cmet.2015.01.003

Cited by 448Metabolism, Diabetes, and CancerDiabetes Treatment and ManagementNatural Antidiabetic Agents Studies

Metformin Action: Concentrations Matter

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He, Ling, Wondisford, Fredric E.·2015·Cell Metabolism

DOI 10.1016/j.cmet.2015.01.003

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Abstract

Metformin has been used for nearly a century and is now the most widely prescribed oral anti-diabetic agent worldwide. Yet how metformin acts remains only partially understood and controversial. One key reason may be that almost all previous studies were conducted with supra-pharmacological concentrations (doses) of metformin, 10-100 times higher than maximally achievable therapeutic concentrations found in patients with type 2 diabetes mellitus.

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Activation of AMPK by metformin has been observed at much lower metformin concentrations in comparable cell culture protocols using concentrations within the upper limits of therapeutic plasma levels.
“activation of AMPK by metformin has been observed at much lower metformin concentrations in comparable cell culture protocols using metformin concentrations that are within the upper limits of its therapeutic plasma levels (4, 134).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [4]
In both Arunachalam et al. and Ghosh et al., 50 μM metformin was used and justified on the basis that estimates of metformin levels in portal circulation following oral absorption are between 40 and 70 μM.
“In both studies, Arunachalam et al. (110) and Ghosh et al. (111) used 50 μM metformin and justified this concentration on the basis that estimates of metformin levels in the portal circulation following oral absorption are between 40 and 70 μM (4, 181).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [4]

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Authors: He, L., & Wondisford, F. E.
Affiliations: Johns Hopkins University (US)
Corresponding author: Wondisford, Fredric E.
ORCID: He, Ling
Wondisford, Fredric E.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2015-02
Volume: 21
Issue: 2
Pages: 159-162
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2015.01.003
OpenAlex: W2080654617
Cited by: 448
References: 18
Citations by year: 2026: 25 · 2025: 30 · 2024: 39 · 2023: 43 · 2022: 61 · 2021: 57 · 2020: 59 · 2019: 37 · 2018: 41 · 2017: 30 · 2016: 16 · 2015: 10
FWCI: 14.05
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 367 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
Keywords: metformin, type 2 diabetes, mechanism of action, therapeutic drug concentrations, oral antidiabetic drugs, pharmacokinetics
MeSH terms: Animals, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Humans, Metformin

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Metformin Action: Concentrations Matter

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