Observational studyPloS one2016
Metformin Induces Cell Cycle Arrest, Reduced Proliferation, Wound Healing Impairment In Vivo and Is Associated to Clinical Outcomes in Diabetic Foot Ulcer Patients.
Observational study in PloS one, 2016. The graph read 1 number from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. An erratum has been issued. Cited by 37 papers.
What it found
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Read, but not usablea number the graph found but could not read as for or against
Unexpectedly, as shown in Fig 5D, when analyzing for differences in the proportion of subjects with amputation, a significantly higher proportion of subjects without amputation were on metformin treatment, suggesting that metformin treatment is protective of amputation (OR = 0.30 CI = 0.1-0.9 P<0.05).
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Where it lands on the map
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What it adds to each cell
For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.
Metformin×cardiovascular events
No readable resultOpen on the map →What to test next →5 readable studies in this cell: 4 favour the treatment, 1 find no difference, 0 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
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
37 citing papers in PubMed, 60 citations in OpenAlex.
- Hsa_circ_0006969 aggravates keratinocytes from high-glucose injury by sponging miR-375 to promote USP10 and SCD expression.Functional & integrative genomics · 2026Article
- Metformin in skin diseases: the role of gut microbiota and immune response.Pharmacological reports : PR · 2026Review
- Metformin administration improves adverse outcomes in older adult burn patients: a single-centre cohort study.npj aging · 2025Article
- 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
- Comparison of topical hypericum perforatum and metformin effectiveness in wound healing in streptozotocin-induced diabetic rats.Frontiers in endocrinology · 2025Article
- Skin manifestations in diabetes-what is new?Frontiers in medicine · 2025Review
- Metformin and the risks of cellulitis, foot infections, and amputation in patients with type 2 diabetes.Journal of the Chinese Medical Association : JCMA · 2024Article
- Treatment of type 2 diabetes mellitus with stem cells and antidiabetic drugs: a dualistic and future-focused approach.Human cell · 2024Review
- The Mechanism of Pyroptosis and Its Application Prospect in Diabetic Wound Healing.Journal of inflammation research · 2024Review
- Review
- In Vitro and In Ovo Evaluation of the Potential Hepatoprotective Effect of Metformin.Medicina (Kaunas, Lithuania) · 2022Article
- Topical application of metformin accelerates cutaneous wound healing in streptozotocin-induced diabetic rats.Molecular biology reports · 2022Article
- Diabetes Mellitus and Periodontitis Share Intracellular Disorders as the Main Meeting Point.Cells · 2021Review
- Growth Factors, Reactive Oxygen Species, and Metformin-Promoters of the Wound Healing Process in Burns?International journal of molecular sciences · 2021Review
- Inhibiting Hyper-O-GlcNAcylation of c-Myc accelerate diabetic wound healing by alleviating keratinocyte dysfunction.Burns & trauma · 2021Article
- Glucose 6-phosphate dehydrogenase inhibition sensitizes melanoma cells to metformin treatment.Translational oncology · 2020Article
- Antidiabetic drug metformin affects the developmental competence of cleavage-stage embryos.Journal of assisted reproduction and genetics · 2020Article
- Electric field down-regulates CD9 to promote keratinocytes migration through AMPK pathway.International journal of medical sciences · 2020Article
- Evaluation of Factors Affecting the Severity of Diabetic Foot Ulcer in Patients with Diabetes Referred to a Diabetes Centre in Kermanshah.Diabetes, metabolic syndrome and obesity : targets and therapy · 2020Article
- Metformin promotes susceptibility to experimental Leishmania braziliensis infection.Memorias do Instituto Oswaldo Cruz · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The marked sentences are the ones the graph read a number from.
backgroundSeveral epidemiological studies in diabetic patients have demonstrated a protective effect of metformin to the development of several types of cancer. The underlying mechanisms of such phenomenon is related to the effect of metformin on cell proliferation among which, mTOR, AMPK and other targets have been identified. However, little is known about the role that metformin treatment have on other cell types such as keratinocytes and whether exposure to metformin of these cells might have serious repercussions in wound healing delay and in the development of complications in diabetic patients with foot ulcers or in their exacerbation. MATERIAL AND
methodsHaCaT Cells were exposed to various concentrations of metformin and cell viability was evaluated by a Resazurin assay; Proliferation was also evaluated with a colony formation assay and with CFSE dilution assay by flow cytometry. Cell cycle was also evaluated by flow cytometry by PI staining. An animal model of wound healing was used to evaluate the effect of metformin in wound closure. Also, an analysis of patients receiving metformin treatment was performed to determine the effect of metformin treatment on the outcome and wound area. Statistical analysis was performed on SPSS v. 18 and GraphPad software v.5.
resultsMetformin treatment significantly reduces cell proliferation; colony formation and alterations of the cell cycle are observed also in the metformin treated cells, particularly in the S phase. There is a significant increase in the area of the wound of the metformin treated animals at different time points (P<0.05). There is also a significant increase in the size and wound area of the patients with diabetic foot ulcers at the time of hospitalization. A protective effect of metformin was observed for amputation, probably associated with the anti inflammatory effects reported of metformin.
conclusionsMetformin treatment reduces cell proliferation and reduces wound healing in an animal model and affects clinical outcomes in diabetic foot ulcer patients. Chronic use of this drug should be further investigated to provide evidence of their security in association with DFU.
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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.