Evidence mapPaperPMID 32897388Full record

ReviewEndocrine reviews2021

Cellular and Molecular Mechanisms of Metformin Action.

Traci E LaMoia, Gerald I Shulman

2 registry-linked trialsOpen access · hybridFull text readReview
In one paragraph

Review in Endocrine reviews, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 398 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
398citing papers in PubMed, 7 pooled it
23.9field-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.

NCT06611501 phase2active not recruitingnot on this mapstarted 2025, after this paper: background citation

Glycemic Regulation as Endometriosis Adjunct Treatment

TypeinterventionalSponsorBoston Children's HospitalRan2025 to 2027Enrolled14ConditionsPelvic Pain, EndometriosisArmsMetformin Hydrochloride, Placebo
NCT07760883 recruitingnot on this map

Effect of Metformin in Individuals With Type 2 Diabetes According to SLC16A11 Risk Variant Carrier Status

TypeobservationalSponsorInstituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranRan2020 to 2027Enrolled154ConditionsDiabetes Type 2
3 · Its place in the literature

Who cites it

398 citing papers in PubMed, 7 syntheses or guidelines pooled it, 703 citations in OpenAlex.

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338 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.

Traci E LaMoiaDepartment of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.
Gerald I ShulmanDepartment of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.
Yale University · US

Funding

Yale Diabetes Research CenterP30DK045735 · YALE UNIVERSITY · 1993 to 2025
$10.2M
Yale Clinical and Translational Science AwardUL1TR001863 · YALE UNIVERSITY · 2025 to 2025
$9.9M
INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDT32GM007324 · YALE UNIVERSITY · 1987 to 2005
$1.3M
Dual-specificity phosphatase action in muscle diseaseR01AR080152 · NIAMS · YALE UNIVERSITY · 2022 to 2025
$1.0M
Development of Controlled Release Mitochondrial Protonophore (CRMP) as a Novel Treatment for Type-2 Diabetes and Non-Alcoholic Steatohepatitis in Dysmetabolic Non-Human PrimatesR01DK119968 · NIDDK · YALE UNIVERSITY · PI GERALD I SHULMAN · 2023 to 2023
$532k
NCATS NIH HHS UL1 TR001863NIAMS NIH HHS R01 AR080152NIDDK NIH HHS F31 DK126362NIDDK NIH HHS P30 DK045735NIDDK NIH HHS R01 DK113984NIDDK NIH HHS R01 DK114793NIDDK NIH HHS R01 DK116774NIDDK NIH HHS R01 DK119968NIDDK NIH HHS RC2 DK120534NIGMS NIH HHS T32 GM007324
6 · The paper itself

Abstract

Metformin is a first-line therapy for the treatment of type 2 diabetes, due to its robust glucose-lowering effects, well-established safety profile, and relatively low cost. While metformin has been shown to have pleotropic effects on glucose metabolism, there is a general consensus that the major glucose-lowering effect in patients with type 2 diabetes is mostly mediated through inhibition of hepatic gluconeogenesis. However, despite decades of research, the mechanism by which metformin inhibits this process is still highly debated. A key reason for these discrepant effects is likely due to the inconsistency in dosage of metformin across studies. Widely studied mechanisms of action, such as complex I inhibition leading to AMPK activation, have only been observed in the context of supra-pharmacological (>1 mM) metformin concentrations, which do not occur in the clinical setting. Thus, these mechanisms have been challenged in recent years and new mechanisms have been proposed. Based on the observation that metformin alters cellular redox balance, a redox-dependent mechanism of action has been described by several groups. Recent studies have shown that clinically relevant (50-100 μM) concentrations of metformin inhibit hepatic gluconeogenesis in a substrate-selective manner both in vitro and in vivo, supporting a redox-dependent mechanism of metformin action. Here, we review the current literature regarding metformin's cellular and molecular mechanisms of action.

Indexed as

AnimalsDiabetes Mellitus, Type 2GluconeogenesisGlucoseHumansHypoglycemic AgentsMetforminGlucoseHypoglycemic AgentsMetforminhepatic gluconeogenesismetforminredoxtype 2 diabetes

Identifiers

PMID32897388
PMCPMC7846086
OpenAlexW3084144806

What Socratic holds

Textfull text, public
LicenceCC BY
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 Socratic graph.