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Metformin Therapy and Risk of Cancer in Patients with Type 2 Diabetes: Systematic Review
Open accessAbstract
AIMS/HYPOTHESIS: Diabetes treatments were related with either an increased or reduced risk of cancer. There is ongoing debate about a potential protective action of metformin. To summarize evidence on the association between metformin and risk of cancer and cancer mortality in patients with diabetes. DATA SOURCE: MEDLINE and EMBASE (January 1966-April 2012). We selected randomized studies comparing metformin and other hypoglycaemic agents and observational studies exploring the association between exposure to metformin and cancer. Outcomes were cancer mortality, all malignancies and site-specific cancers. RESULTS: Of 25307 citations identified, 12 randomized controlled trials (21,595 patients) and 41 observational studies (1,029,389 patients) met the inclusion criteria. In observational studies there was a significant association of exposure to metformin with the risk of cancer death [6 studies, 24,410 patients, OR:0.65, 95%CI: 0.53-0.80], all malignancies [18 studies, 561,836 patients, OR:0.73, 95%CI: 0.61-0.88], liver [8 studies, 312,742 patients, OR:0.34; 95%CI: 0.19-0.60] colorectal [12 studies, 871,365 patients, OR:0.83, 95%CI: 0.74-0.92], pancreas [9 studies, 847,248 patients, OR:0.56, 95%CI: 0.36-0.86], stomach [2 studies, 100701 patients, OR:0.83, 95%CI: 0.76-0.91], and esophagus cancer [2 studies, 100694 patients, OR:0.90, 95%CI: 0.83-0.98]. No significant difference of risk was observed in randomized trials. Metformin was not associated with the risk of: breast cancer, lung cancer, ovarian cancer, uterus cancer, prostate cancer, bladder cancer, kidney cancer, and melanoma. CONCLUSIONS/INTERPRETATION: Results suggest that Metformin might be associated with a significant reduction in the risk of cancer and cancer-related mortality. Randomized trials specifically designed to evaluate the efficacy of metformin as an anticancer agent are warranted.
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“long-term use of metformin in type 2 diabetes patients has been linked to a decline in tumor incidence and a reduced rate of cancer-related deaths.192–196”
From Drug repurposing for cancer therapy (2024) · cites this paper as [193]
Experimental — accuracy not yet measuredIn the citing paper
“Furthermore, retrospective clinical studies have found that metformin use is associated with improved cancer outcomes, reductions in cancer incidence, and decreased cancer mortality (Evans et al., 2005; Franciosi et al., 2013; Gandini et al., 2014; Lee et al., 2012; Noto et al., 2012).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Franciosi et al., 2013
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“this finding has subsequently been confirmed in several other studies(7–10).”
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“Originally introduced for the treatment of diabetes, metformin is now gaining attention as a potential anti-cancer agent (7–10) (Figure 1).”
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Epidemiology of Hepatocellular Carcinoma
McGlynn, K. A., Petrick, J. L., & El‐Serag, H. B. (2020) · Hepatology · doi:10.1002/hep.31288 · Cited by 2,200
Revisiting STAT3 signalling in cancer: new and unexpected biological functions
Yu, H., Lee, H., Herrmann, A., Buettner, R., & Jove, R. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3818 · Cited by 2,137
Pancreatic Adenocarcinoma, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology
Tempero, M. A., Malafa, M. P., Al-Hawary, M. M., Behrman, S. W., Benson, A. B., Cardin, D. B., Chiorean, E. G., Chung, V. M., Czito, B. G., Chiaro, M. D., et al. (2021) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2021.0017 · Cited by 1,356
Tilg, H., Moschen, A. R., & Roden, M. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.147 · Cited by 1,002
Targeting Metabolism for Cancer Therapy
Luengo, A., Gui, D. Y., & Vander Heiden, M. G. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.08.028 · Cited by 971
Metadata
- Authors
- Franciosi, M., Lucisano, G., Lapice, E., Strippoli, G. F. M., Pellegrini, F., & Nicolucci, A.
- Affiliations
- University of Naples Federico II (IT)
- The University of Sydney (AU)
- Corresponding author
- Franciosi, Monica
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-08-02
- Volume
- 8
- Issue
- 8
- Pages
- e71583
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3732236
- OpenAlex
- W2081540191
- Cited by
- 428
- References
- 89
- Citations by year
- 2026: 8 · 2025: 18 · 2024: 19 · 2023: 27 · 2022: 18 · 2021: 29 · 2020: 31 · 2019: 36 · 2018: 31 · 2017: 44 · 2016: 51 · 2015: 59 · 2014: 52 · 2013: 5
- FWCI
- 5.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- type 2 diabetes, cancer risk, cancer mortality, liver cancer, colorectal cancer, pancreatic cancer, gastric cancer, esophageal cancer, site-specific cancer, chemoprevention, antidiabetic drugs, drug safety, randomized controlled trials, observational studies, breast cancer, lung cancer, ovarian cancer, prostate cancer, bladder cancer, kidney cancer, melanoma
- MeSH terms
- Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Metformin, Neoplasms, Risk Factors, Meta-Analysis as Topic, Randomized Controlled Trials as Topic, Diabetes Complications
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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