Evidence mapPaperPMID 25218668Full record

Trial reportClinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association2015

Metformin does not reduce markers of cell proliferation in esophageal tissues of patients with Barrett's esophagus.

Amitabh Chak, Navtej S Buttar, Nathan R Foster, Drew K Seisler, Norman E Marcon, Robert Schoen, Marcia R Cruz-Correa, Gary W Falk, Prateek Sharma, Chin Hur and 8 more

Registry-linked trialOpen access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01447927 (Randomized Double Blind Placebo Controlled Trial of Barrett's Esophagus Chemoprevention With Metformin), which is not on this map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 11% 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.

NCT01447927 phase2completednot on this map

Randomized Double Blind Placebo Controlled Trial of Barrett's Esophagus Chemoprevention With Metformin

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2012 to 2013Enrolled93ConditionsBarrett Esophagus, Esophageal CancerArmsmetformin hydrochloride, placebo
3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.

  1. Pooled it
  2. Randomized Controlled Trial of the Gastrin/CCKCancer prevention research (Philadelphia, Pa.) · 2021
    Trial
  3. Trial
  4. Trial
  5. Clinical Study of Ursodeoxycholic Acid in Barrett's Esophagus Patients.Cancer prevention research (Philadelphia, Pa.) · 2016
    Trial
  6. Article
  7. Drug repurposing for cancer therapy.Signal transduction and targeted therapy · 2024
    Review
  8. Metformin: A Dual-Role Player in Cancer Treatment and Prevention.International journal of molecular sciences · 2024
    Review
  9. Review
  10. Review
  11. Review
  12. Improving outcomes in patients with oesophageal cancer.Nature reviews. Clinical oncology · 2023
    Review
  13. Article
  14. Article
  15. Review
  16. Chemoprevention in Barrett's esophagus and esophageal adenocarcinoma.Therapeutic advances in gastroenterology · 2021
    Review
  17. Review
  18. Chemoprevention of esophageal adenocarcinoma.Gastroenterology report · 2020
    Review
  19. Review
  20. Predictors of Progression in Barrett's Esophagus.Current treatment options in gastroenterology · 2019
    Review
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

18 authors at 10 institutions in 3 countries.

Amitabh ChakDepartment of Gastroenterology and Hepatology, University Hospitals Case Medical Center, Cleveland, Ohio. Electronic address: amitabh.chak@UHhospitals.org.
Navtej S ButtarDepartment of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Nathan R FosterDepartment of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
Drew K SeislerDepartment of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
Norman E MarconDepartment of Medicine, Gastroenterology, St Michael's Hospital, Toronto, Ontario, Canada.
Robert SchoenDepartment of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania.
Marcia R Cruz-CorreaDepartment of Gastroenterology Oncology at UPR Cancer Center, University of Puerto Rico, San Juan, Puerto Rico.
Gary W FalkDepartment of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Prateek SharmaDepartment of Gastroenterology, Hepatology and Motility, Kansas City VA, Kansas City, Missouri.
Chin HurGastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
David A KatzkaDepartment of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Luz M RodriguezDivision of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Ellen RichmondDivision of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Anamay N SharmaDepartment of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Thomas C SmyrkDepartment of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota.
Sumithra J MandrekarDepartment of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
Paul J LimburgDepartment of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Cancer Prevention Network
Mayo Clinic · USWinnMed · USKansas City VA Medical Center · USMassachusetts General Hospital · USNational Cancer Institute · USNational Institutes of Health · USUniversity Hospitals Case Medical Center · USUniversity of Pennsylvania · USUniversity of Pittsburgh · USUniversity of Puerto Rico System · PR

Funding

Transgenic and Knockout Shared ResourceP30CA015083 · MAYO CLINIC ROCHESTER · 1985 to 2025
$27.9M
PHASE 1 AND PHASE 2 CLINICAL TRIALS OF CANCER CHEMOPREVENTIVE AGENTS -261035000N01CN035000 · UNIVERSITY OF SOUTHERN CALIFORNIA · 1985 to 2004
NCATS NIH HHS UL1 TR000135NCI NIH HHS N01 CN035000NCI NIH HHS N01-CN-35000NCI NIH HHS P30 CA015083NCI NIH HHS P50 CA150964NCRR NIH HHS 1 UL1 RR024150-01NCRR NIH HHS UL1 RR024150
6 · The paper itself

Abstract

BACKGROUND &

aimsObesity is associated with neoplasia, possibly via insulin-mediated cell pathways that affect cell proliferation. Metformin has been proposed to protect against obesity-associated cancers by decreasing serum insulin. We conducted a randomized, double-blind, placebo-controlled, phase 2 study of patients with Barrett's esophagus (BE) to assess the effect of metformin on phosphorylated S6 kinase (pS6K1), a biomarker of insulin pathway activation.

methodsSeventy-four subjects with BE (mean age, 58.7 years; 58 men [78%; 52 with BE >2 cm [70%]) were recruited through 8 participating organizations of the Cancer Prevention Network. Participants were randomly assigned to groups given metformin daily (increasing to 2000 mg/day by week 4, n = 38) or placebo (n = 36) for 12 weeks. Biopsy specimens were collected at baseline and at week 12 via esophagogastroduodenoscopy. We calculated and compared percent changes in median levels of pS6K1 between subjects given metformin vs placebo as the primary end point.

resultsThe percent change in median level of pS6K1 did not differ significantly between groups (1.4% among subjects given metformin vs -14.7% among subjects given placebo; 1-sided P = .80). Metformin was associated with an almost significant reduction in serum levels of insulin (median -4.7% among subjects given metformin vs 23.6% increase among those given placebo, P = .08) as well as in homeostatic model assessments of insulin resistance (median -7.2% among subjects given metformin vs 38% increase among those given placebo, P = .06). Metformin had no effects on cell proliferation (on the basis of assays for KI67) or apoptosis (on the basis of levels of caspase 3).

conclusionsIn a chemoprevention trial of patients with BE, daily administration of metformin for 12 weeks, compared with placebo, did not cause major reductions in esophageal levels of pS6K1. Although metformin reduced serum levels of insulin and insulin resistance, it did not discernibly alter epithelial proliferation or apoptosis in esophageal tissues. These findings do not support metformin as a chemopreventive agent for BE-associated carcinogenesis. ClinicalTrials.gov number, NCT01447927.

Indexed as

AdultAgedAged, 80 and overBarrett EsophagusCell ProliferationDouble-Blind MethodEndoscopy, Digestive SystemEsophageal NeoplasmsFemaleHumansInsulinMaleMetforminMiddle AgedPlacebosProspective StudiesInsulinMetforminPlacebosRibosomal Protein S6 KinasesCancer DevelopmentDiabetes DrugHOMA-IRTumorigenesis

Identifiers

PMID25218668
PMCPMC4362887
OpenAlexW1965316457

What Socratic holds

Textmetadata
LicenceTDM
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.