New Users of Metformin Are at Low Risk of Incident Cancer

By G. Libby, L. Donnelly, P. Donnan, D. Alessi, A. Morris, J. Evans. Diabetes Care, 2009

1,086 citations recorded by the source corpus.

OBJECTIVE The antidiabetic properties of metformin are mediated through its ability to activate the AMP-activated protein kinase (AMPK). Activation of AMPK can suppress tumor formation and inhibit cell growth in addition to lowering blood glucose levels. We tested the hypothesis that metformin reduces the risk of cancer in people with type 2 diabetes. RESEARCH DESIGN AND METHODS In an observational cohort study using record-linkage databases and based in Tayside, Scotland, U.K., we identified people with type 2 diabetes who were new users of metformin in 1994–2003. We also identified a set of diabetic comparators, individually matched to the metformin users by year of diabetes diagnosis, who had never used metformin. In a survival analysis we calculated hazard ratios for diagnosis of cancer, adjusted for baseline characteristics of the two groups using Cox regression. RESULTS Cancer was diagnosed among 7.3% of 4,085 metformin users compared with 11.6% of 4,085 comparators, with median times to cancer of 3.5 and 2.6 years, respectively (P < 0.001). The unadjusted hazard ratio (95% CI) for cancer was 0.46 (0.40–0.53). After adjusting for sex, age, BMI, A1C, deprivation, smoking, and other drug use, there was still a significantly reduced risk of cancer associated with metformin: 0.63 (0.53–0.75). CONCLUSIONS These results suggest that metformin use may be associated with a reduced risk of cancer. A randomized trial is needed to assess whether metformin is protective in a population at high risk for cancer.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/ea270ba1a8b2b5a6b30e00c000549dfa90d9224c

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Citations in the corpus

Metformin and Cancer Risk in Diabetic Patients: A Systematic Review and Meta-analysis (2010, neutral): “Table Sourc Yang e 200 Bowker et al., 200 Popula ite 63 1991-1996 No/Yes 407 10309† 5.4 Monami et al., 200 Hospit ite 69 1998-2005 Yes/No 195 195 6.5 Libby et al., 2009 (Sco Popula ite 66 1994-2003 Yes/Yes 771 8170† 7 Currie et al., 200 Gener ite 64 2000-2005 Yes/No 373 7897† 2.4 Donad 200 Landm…”
Obesity and cancer risk: Emerging biological mechanisms and perspectives. (2019, background): “account for the decrease in cancer risk observed in epidemiologic studies [241, 242].”
The Critical Role of Metabolic Pathways in Aging (2012, background): “Furthermore, there are no data to support a role for metformin in human aging, but it is welltolerated in patients with T2DM and has recently emerged as an anticancer agent (63).”
Metformin as a Tool to Target Aging (2016, positive): “Observational Studies Suggest Metformin Decreases Cancer Incidence Several epidemiologic studies have shown that metformin use is associated with reduced cancer incidence and mortality (Landman et al., 2010; Lee et al., 2011; Libby et al., 2009; Monami et al., 2011; Tseng, 2012).”
Targeting metabolic transformation for cancer therapy (2010, background): “This drug is first and foremost used to treat patients with type 2 diabetes, but a study of patients with diabetes found that those treated with metformin were more likely to be cancer free over 8 years than those on other treatment regime”
Metformin, Independent of AMPK, Inhibits mTORC1 In a Rag GTPase-Dependent Manner (2010, background): “Elucidating the role of mTORC1 in response to energy depletion is critical because of the broad clinical use of the antidiabetic drug metformin (Libby et al., 2009; Shackelford and Shaw, 2009).”
Rapamycin passes the torch: a new generation of mTOR inhibitors (2011, background): “Metformin is a widely prescribed anti-diabetic drug, and epidemiological studies have repeatedly confirmed a lower incidence of a broad range of cancers among diabetic patients taking metformi”
Update on the treatment of type 2 diabetes mellitus. (2016, background): “Cancer incidence: Observational data suggest that metformin decreases cancer incidence [67,68] .”
Cellular and molecular mechanisms of metformin: an overview. (2012, background): “neoplastic diseases and cancer mortality in T2D patients treated with metformin [107-109].”