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.
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.
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.
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.
Randomized Double Blind Placebo Controlled Trial of Barrett's Esophagus Chemoprevention With Metformin
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Metformin: A Dual-Role Player in Cancer Treatment and Prevention: A Comprehensive Systematic Review and Meta-Analysis.Medicina (Kaunas, Lithuania) · 2025Pooled it
- Randomized Controlled Trial of the Gastrin/CCKCancer prevention research (Philadelphia, Pa.) · 2021Trial
- A Phase IIa Trial of Metformin for Colorectal Cancer Risk Reduction among Individuals with History of Colorectal Adenomas and Elevated Body Mass Index.Cancer prevention research (Philadelphia, Pa.) · 2020Trial
- Trial
- Clinical Study of Ursodeoxycholic Acid in Barrett's Esophagus Patients.Cancer prevention research (Philadelphia, Pa.) · 2016Trial
- Was It Worth It? Response Data from >650 US and International Participants in Chemoprevention Trials.Cancer prevention research (Philadelphia, Pa.) · 2026Article
- Drug repurposing for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Metformin: A Dual-Role Player in Cancer Treatment and Prevention.International journal of molecular sciences · 2024Review
- Metformin in Esophageal Carcinoma: Exploring Molecular Mechanisms and Therapeutic Insights.International journal of molecular sciences · 2024Review
- Translating Molecular Biology Discoveries to Develop Targeted Cancer Interception in Barrett's Esophagus.International journal of molecular sciences · 2023Review
- Metformin and cancer hallmarks: shedding new lights on therapeutic repurposing.Journal of translational medicine · 2023Review
- Improving outcomes in patients with oesophageal cancer.Nature reviews. Clinical oncology · 2023Review
- NDUFS3 knockout cancer cells and molecular docking reveal specificity and mode of action of anti-cancer respiratory complex I inhibitors.Open biology · 2022Article
- Metformin and Dementia Risk: A Systematic Review with Respect to Time Related Biases.Journal of Alzheimer's disease reports · 2022Article
- Review
- Chemoprevention in Barrett's esophagus and esophageal adenocarcinoma.Therapeutic advances in gastroenterology · 2021Review
- Visceral Obesity, Metabolic Syndrome, and Esophageal Adenocarcinoma.Frontiers in oncology · 2021Review
- Chemoprevention of esophageal adenocarcinoma.Gastroenterology report · 2020Review
- Current management of Barrett esophagus and esophageal adenocarcinoma.Cleveland Clinic journal of medicine · 2019Review
- Predictors of Progression in Barrett's Esophagus.Current treatment options in gastroenterology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 10 institutions in 3 countries.
Funding
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.
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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.