Evidence map›Paper›PMID 20972533›Full record

ArticleDiabetologia2011

Metformin regulates the incretin receptor axis via a pathway dependent on peroxisome proliferator-activated receptor-α in mice.

A Maida, B J Lamont, X Cao, D J Drucker

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Diabetologia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.

0numbers the graph read from it
0cells of the map it votes in
126citing papers in PubMed
20.2field-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.

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

126 citing papers in PubMed, 285 citations in OpenAlex.

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  12. Metformin Beyond Glycemic Control: Cardiovascular Protection and Diabetes Prevention.Journal of cardiovascular development and disease · 2026
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66 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

A MaidaInstitute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
B J Lamont
X Cao
D J Drucker
University of Toronto · CA

Funding

Canadian Institutes of Health Research MOP82700
6 · The paper itself

Abstract

aims/hypothesisMetformin is widely used for the treatment of type 2 diabetes. Although it reduces hepatic glucose production, clinical studies show that metformin may reduce plasma dipeptidyl peptidase-4 activity and increase circulating levels of glucagon-like peptide 1 (GLP-1). We examined whether metformin exerts glucoregulatory actions via modulation of the incretin axis.

methodsMetformin action was assessed in Glp1r(-/-), Gipr(-/-), Glp1r:Gipr(-/-), Pparα (also known as Ppara)(-/-) and hyperglycaemic obese wild-type mice with or without the GLP-1 receptor (GLP1R) antagonist exendin(9-39). Experimental endpoints included glucose tolerance, plasma insulin levels, gastric emptying and food intake. Incretin receptor expression was assessed in isolated islets from metformin-treated wild-type and Pparα(-/-) mice, and in INS-1 832/3 beta cells with or without peroxisome proliferator-activated receptor (PPAR)-α or AMP-activated protein kinase (AMPK) antagonists.

resultsIn wild-type mice, metformin acutely increased plasma levels of GLP-1, but not those of gastric inhibitory polypeptide or peptide YY; it also improved oral glucose tolerance and reduced gastric emptying. Metformin significantly improved oral glucose tolerance despite loss of incretin action in Glp1r(-/-), Gipr(-/-) and Glp1r(-/-) :Gipr(-/-) mice, and in wild-type mice fed a high-fat diet and treated with exendin(9-39). Levels of mRNA transcripts for Glp1r, Gipr and Pparα were significantly increased in islets from metformin-treated mice. Metformin directly increased Glp1r expression in INS-1 beta cells via a PPAR-α-dependent, AMPK-independent mechanism. Metformin failed to induce incretin receptor gene expression in islets from Pparα(-/-) mice. CONCLUSIONS/

interpretationAs metformin modulates multiple components of the incretin axis, and enhances expression of the Glp1r and related insulinotropic islet receptors through a mechanism requiring PPAR-α, metformin may be mechanistically well suited for combination with incretin-based therapies.

Indexed as

AnimalsCell LineDiabetes Mellitus, Type 2Dipeptidyl Peptidase 4EatingGastric Inhibitory PolypeptideGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorHypoglycemic AgentsMaleMetforminMiceMice, Inbred C57BLMice, Mutant StrainsPeptide FragmentsPPAR alphaDipeptidyl Peptidase 4exendin (9-39)Gastric Inhibitory Polypeptidegastric inhibitory polypeptide receptorGlp1r protein, mouseGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorHypoglycemic AgentsMetforminPeptide FragmentsPPAR alphaReceptors, Gastrointestinal HormoneReceptors, Glucagon

Identifiers

PMID20972533
OpenAlexW2015569637

What OpenQuestion 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 OpenQuestion graph.