Evidence mapPaperPMID 12086935Full record

Trial reportDiabetes2002

Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes.

Nicolas Musi, Michael F Hirshman, Jonas Nygren, Monika Svanfeldt, Peter Bavenholm, Olav Rooyackers, Gaochao Zhou, Joanne M Williamson, Olle Ljunqvist, Suad Efendic and 3 more

3 registry-linked trialsOpen access · bronzeAbstract readClinical Trial
PubMed Publisher
In one paragraph

Trial report in Diabetes, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 293 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
293citing papers in PubMed, 2 pooled it
8.4field-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.

NCT04626089 phase2withdrawnstarted 2021, after this paper: background citation

Adaptive Study for Efficacy and Safety of Metformin Glycinate for the Treatment of Patients With MS and DM2, Hospitalized With Severe Acute Respiratory Syndrome Secondary to SARS-CoV-2. Randomized, Double-Blind, Phase IIIb.

Ran2021Enrolled0Registered outcomes12Posted comparisons0ConditionsMetabolic Syndrome, Severe Acute Respiratory Syndrome Coronavirus 2, Type 2 DiabetesArmsMetformin glycinate, Placebo Oral Tablet
Open the trial in the graph
NCT04841668 completedstarted 2021, after this paper: background citation

Gut-Brain-axis: Targets for Improvement of Cognition in the Elderly

Ran2021Enrolled50Registered outcomes51Posted comparisons0ConditionsType 2 Diabetes MellitusArmsMetformin
Open the trial in the graph
NCT04625985 phase2completednot on this mapstarted 2020, after this paper: background citation

Adaptive Study to Demonstrate Efficacy and Safety of Metformin Glycinate for the Treatment of Hospitalized Patients With Severe Acute Respiratory Syndrome Secondary to SARS-CoV-2. Randomized, Double-Blind, Phase IIIb

TypeinterventionalSponsorLaboratorios Silanes S.A. de C.V.Ran2020 to 2021Enrolled20ConditionsSevere Acute Respiratory Syndrome Coronavirus 2ArmsMetformin Glycinate, Placebo oral tablet
3 · Its place in the literature

Who cites it

293 citing papers in PubMed, 2 syntheses or guidelines pooled it, 801 citations in OpenAlex.

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  18. Pharmacogenetics and Molecular Ancestry ofPharmaceuticals (Basel, Switzerland) · 2025
    Article
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233 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

13 authors at 6 institutions in 2 countries.

Nicolas MusiResearch Division, Joslin Diabetes Center, Brigham and Women's Hospital and Harvard Medical School, One Joslin Place, Boston, MA 02215, USA. laurie.goodyear@joslin.harvard.edu
Michael F Hirshman
Jonas Nygren
Monika Svanfeldt
Peter Bavenholm
Olav Rooyackers
Gaochao Zhou
Joanne M Williamson
Olle Ljunqvist
Suad Efendic
David E Moller
Anders Thorell
Laurie J Goodyear
Merck & Co., Inc., Rahway, NJ, USA (United States) · USErsta sjukhus · SEHarvard University · USJoslin Diabetes Center · USKarolinska Institutet · SEKarolinska University Hospital · SE

Funding

EXERCISE REGULATION OF GLUCOSE UPTAKE IN SKELETAL MUSCLER01AR045670 · JOSLIN DIABETES CENTER · 1998 to 2005
$2.1M
NIAMS NIH HHS AR 45670
6 · The paper itself

Abstract

Metformin is an effective hypoglycemic drug that lowers blood glucose concentrations by decreasing hepatic glucose production and increasing glucose disposal in skeletal muscle; however, the molecular site of metformin action is not well understood. AMP-activated protein kinase (AMPK) activity increases in response to depletion of cellular energy stores, and this enzyme has been implicated in the stimulation of glucose uptake into skeletal muscle and the inhibition of liver gluconeogenesis. We recently reported that AMPK is activated by metformin in cultured rat hepatocytes, mediating the inhibitory effects of the drug on hepatic glucose production. In the present study, we evaluated whether therapeutic doses of metformin increase AMPK activity in vivo in subjects with type 2 diabetes. Metformin treatment for 10 weeks significantly increased AMPK alpha2 activity in the skeletal muscle, and this was associated with increased phosphorylation of AMPK on Thr172 and decreased acetyl-CoA carboxylase-2 activity. The increase in AMPK alpha2 activity was likely due to a change in muscle energy status because ATP and phosphocreatine concentrations were lower after metformin treatment. Metformin-induced increases in AMPK activity were associated with higher rates of glucose disposal and muscle glycogen concentrations. These findings suggest that the metabolic effects of metformin in subjects with type 2 diabetes may be mediated by the activation of AMPK alpha2.

Indexed as

AMP-Activated Protein KinasesBlood GlucoseDiabetes Mellitus, Type 2Fatty Acids, NonesterifiedFemaleGlycated HemoglobinHumansHypoglycemic AgentsInsulinKineticsLipidsMaleMetforminMiddle AgedMultienzyme ComplexesMuscle, SkeletalAMP-Activated Protein KinasesBlood GlucoseFatty Acids, NonesterifiedGlycated HemoglobinHypoglycemic AgentsInsulinLipidsMetforminMultienzyme ComplexesPRKAA2 protein, humanProtein Serine-Threonine Kinases

Identifiers

PMID12086935
OpenAlexW2122649002

What Socratic holds

Texttitle and abstract
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.