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Cited by 430Metabolism, Diabetes, and CancerDiabetes Treatment and ManagementPancreatic and Hepatic Oncology Research

Metformin Therapy and Risk of Cancer in Patients with Type 2 Diabetes: Systematic Review

Open access
Franciosi, Monica, Lucisano, Giuseppe, Lapice, Emanuela, Strippoli, Giovanni F. M., Pellegrini, Fabio, Nicolucci, Antonio·2013·PLoS ONE
DOI 10.1371/journal.pone.0071583PMC PMC3732236
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Abstract

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 is linked to a decline in tumor incidence and a reduced rate of cancer-related deaths.

    “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]

    The Results sections on any malignancy and cancer mortality report lower risks among metformin users in observational studies of people with type 2 diabetes. However, the Discussion (Strengths and weaknesses) says treatment-duration details were incomplete, so the review does not establish the claim specifically for long-term use; the Results also found no significant difference in randomized trials. (LLM, conf=0.88)

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  • Retrospective clinical studies have found that metformin use is associated with improved cancer outcomes, reductions in cancer incidence, and decreased cancer mortality.

    “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

  • This finding has subsequently been confirmed in several other studies.

    “this finding has subsequently been confirmed in several other studies(7–10).”

    From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [8]

  • Metformin is now gaining attention as a potential anti-cancer agent.

    “Originally introduced for the treatment of diabetes, metformin is now gaining attention as a potential anti-cancer agent (7–10) (Figure 1).”

    From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [8]

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  1. [82]Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C et al. (2009) Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breastcancer. J Clin Oncol 27: 3297– 3302. doi: 10.1200/JCO.2009.19.6410. PubMed: 19487376. 19487376 PMC2736070 · DOI · Paper page

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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
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-08-02
Volume
8
Issue
8
Pages
e71583
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0071583
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
Licence
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

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