Evidence map›Paper›PMID 28530702›Full record

Trial reportNature medicine2017

Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug.

Hao Wu, Eduardo Esteve, Valentina Tremaroli, Muhammad Tanweer Khan, Robert Caesar, Louise Mannerås-Holm, Marcus Ståhlman, Lisa M Olsson, Matteo Serino, Mercè Planas-Fèlix and 8 more

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06611501 (Glycemic Regulation as Endometriosis Adjunct Treatment), which is not on this map. Cited by 911 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
911citing papers in PubMed, 6 pooled it
–field-weighted citation impact
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
3 · Its place in the literature

Who cites it

911 citing papers in PubMed, 6 syntheses or guidelines pooled it.

  1. Pooled it
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  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Trial
  8. Trial
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  12. Review
  13. Article
  14. Review
  15. Obstetric Pharmacomicrobiomics.Clinical pharmacology and therapeutics · 2026
    Review
  16. Pharmacomicrobiomics-driven targeted drug delivery for precision microbiome modulation.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026
    Review
  17. Review
  18. Article
  19. Review
  20. Article

851 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Hao WuDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Eduardo EsteveDepartment of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona, Hospital Josep Trueta, Girona, Spain.
Valentina TremaroliDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Muhammad Tanweer KhanDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Robert CaesarDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Louise Mannerås-HolmDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Marcus StåhlmanDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Lisa M OlssonDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Matteo SerinoIRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France.
Mercè Planas-FèlixBarcelona Supercomputing Center (BSC), Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona, Spain.
Gemma XifraDepartment of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona, Hospital Josep Trueta, Girona, Spain.
Josep M MercaderBarcelona Supercomputing Center (BSC), Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona, Spain.
David TorrentsBarcelona Supercomputing Center (BSC), Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona, Spain.
Rémy BurcelinInstitut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France.
Wifredo RicartDepartment of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona, Hospital Josep Trueta, Girona, Spain.
Rosie PerkinsDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
José Manuel Fernàndez-RealDepartment of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona, Hospital Josep Trueta, Girona, Spain.
Fredrik BäckhedDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metformin is widely used in the treatment of type 2 diabetes (T2D), but its mechanism of action is poorly defined. Recent evidence implicates the gut microbiota as a site of metformin action. In a double-blind study, we randomized individuals with treatment-naive T2D to placebo or metformin for 4 months and showed that metformin had strong effects on the gut microbiome. These results were verified in a subset of the placebo group that switched to metformin 6 months after the start of the trial. Transfer of fecal samples (obtained before and 4 months after treatment) from metformin-treated donors to germ-free mice showed that glucose tolerance was improved in mice that received metformin-altered microbiota. By directly investigating metformin-microbiota interactions in a gut simulator, we showed that metformin affected pathways with common biological functions in species from two different phyla, and many of the metformin-regulated genes in these species encoded metalloproteins or metal transporters. Our findings provide support for the notion that altered gut microbiota mediates some of metformin's antidiabetic effects.

Indexed as

AnimalsBile Acids and SaltsDiabetes Mellitus, Type 2DNA, BacterialDouble-Blind MethodFatty Acids, VolatileFecal Microbiota TransplantationFecesFemaleGastrointestinal MicrobiomeGerm-Free LifeGlucose Tolerance TestHumansHypoglycemic AgentsIn Vitro TechniquesMaleBile Acids and SaltsDNA, BacterialFatty Acids, VolatileHypoglycemic AgentsMetformin

Identifiers

PMID28530702

What OpenQuestion 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 OpenQuestion graph.