SynthesisPloS one2015
Anti-tumor effects of metformin in animal models of hepatocellular carcinoma: a systematic review and meta-analysis.
Synthesis in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- What has preclinical systematic review ever done for us?BMJ open science · 2022Pooled it
- Meta-analysis of studies using metformin as a reducer for liver cancer risk in diabetic patients.Medicine · 2017 · on this mapPooled it
- Fasting in combination with the cocktail Sorafenib:Metformin blunts cellular plasticity and promotes liver cancer cell death via poly-metabolic exhaustion.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Association of perioperative use of statins, metformin, and aspirin with recurrence after curative liver resection in patients with hepatocellular carcinoma: A propensity score matching analysis.Cancer medicine · 2023Article
- Antitumor Activity of Metformin Combined with Locoregional Therapy for Liver Cancer: Evidence and Future Directions.Cancers · 2023Review
- Use of Metformin and Survival in Patients with Hepatocellular Carcinoma (HCC) Undergoing Liver Directed Therapy: Analysis of a Nationwide Cancer Registry.Cardiovascular and interventional radiology · 2023Article
- Improved Tumor Response in Patients on Metformin Undergoing Yttrium-90 Radioembolization Segmentectomy for Hepatocellular Carcinoma.Cardiovascular and interventional radiology · 2021Article
- Improved Tumor Response in Patients on Metformin Undergoing Yttrium-90 Radioembolization Segmentectomy for Hepatocellular Carcinoma.Cardiovascular and interventional radiology · 2021Article
- High HbA1c is a risk factor for complications after hepatectomy and influences for hepatocellular carcinoma without HBV and HCV infection.Hepatobiliary surgery and nutrition · 2021Article
- Metformin exerts anti-cancerogenic effects and reverses epithelial-to-mesenchymal transition trait in primary human intrahepatic cholangiocarcinoma cells.Scientific reports · 2021Article
- Metformin Improves Biochemical and Pathophysiological Changes in Hepatocellular Carcinoma with Pre-Existed Diabetes Mellitus Rats.Pathogens (Basel, Switzerland) · 2021Article
- Article
- Transcriptomic landscape profiling of metformin-treated healthy mice: Implication for potential hypertension risk when prophylactically used.Journal of cellular and molecular medicine · 2020Article
- Therapeutic effect of regulating autophagy in spinal cord injury: a network meta-analysis of direct and indirect comparisons.Neural regeneration research · 2020Article
- The cytotoxicity of gallium maltolate in glioblastoma cells is enhanced by metformin through combined action on mitochondrial complex 1.Oncotarget · 2020Article
- Metformin modifies disparity in hepatocellular carcinoma incidence in men with type 2 diabetes but without chronic liver diseases.Cancer medicine · 2019Article
- Metformin modulates innate immune-mediated inflammation and early progression of NAFLD-associated hepatocellular carcinoma in zebrafish.Journal of hepatology · 2019Article
- Metabolic factors affecting hepatocellular carcinoma in steatohepatitis.Liver international : official journal of the International Association for the Study of the Liver · 2019Article
- MicroRNA-Based Prophylaxis in a Mouse Model of Cirrhosis and Liver Cancer.Molecular therapy. Nucleic acids · 2019Article
- Dipeptidyl Peptidase 4 Inhibitors Reduce Hepatocellular Carcinoma by Activating Lymphocyte Chemotaxis in Mice.Cellular and molecular gastroenterology and hepatology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSeveral studies have reported that metformin can reduce the risk of hepatocellular carcinoma (HCC) in diabetes patients. However, the direct anti-HCC effects of metformin have hardly been studied in patients, but have been extensively investigated in animal models of HCC. We therefore performed a systematic review and meta-analysis of animal studies evaluating the effects of metformin on HCC.
methodsWe collected the relevant studies by searching EMBASE, Medline (OvidSP), Web of Science, Scopus, PubMed Publisher, and Google Scholar. Studies were included according to the following inclusion criteria: HCC, animal study, and metformin intervention. Study quality was assessed using SYRCLE's risk of bias tool. A meta-analysis was performed for the outcome measures: tumor growth (tumor volume, weight and size), tumor number and incidence.
resultsThe search resulted in 573 references, of which 13 could be included in the review and 12 included in the meta-analysis. The study characteristics of the included studies varied considerably. Two studies used rats, while the others used mice. Only one study used female animals, nine used male, and three studies didn't mention the gender of animals in their experiments. The quality of the included studies was low to moderate based on the assessment of their risk of bias. The meta-analysis showed that metformin significantly inhibited the growth of HCC tumour (SMD -2.20[-2.96,-1.43]; n=16), but no significant effect on the number of tumors (SMD-1.05[-2.13,0.03]; n=5) or the incidence of HCC was observed (RR 0.62[0.33,1.16]; n=6). To investigate the potential sources of significant heterogeneities found in outcome of tumor growth (I2=81%), subgroup analyses of scales of growth measures and of types of animal models used were performed.
conclusionMetformin appears to have a direct anti-HCC effect in animal models. Although the intrinsic limitations of animal studies, this systematic review could provide an important reference for future preclinical animal trials of good quality and clinical development.
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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 OpenQuestion graph.