Metformin use reduced the overall risk of cancer in diabetic patients: A study based on the Korean NHIS-HEALS cohort

Kim, Yeseul; Choi, Eun‐A; Lee, Jae-woo; Kim, Yonghwan; You, Hyo-Sun; Han, Ye-Eun; Kim, Hyeong-Seop; Bae, Yoon-Jong; Kang, Hee-Taik; Kim, Joungyoun

doi:10.1016/j.numecd.2020.05.010

Cited by 16 publications

(11 citation statements)

References 36 publications

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“…Furthermore, in view of its safe profile and low cost, metformin is also used to ameliorate IR even in nondiabetic patients, such as PCOS patients. Apart from its glucose-lowering effects and the clinically proven benefits on both pregnancy rates and hyperandrogenic traits of PCOS, there is increasing epidemiologic evidence that patients using metformin have reduced risk of developing cancer, thus highlighting the preventive and therapeutic potential of this drug against malignancies [ 294 , 295 ]. In this regard, post-menopausal diabetic women under metformin treatment had lower risk of invasive breast cancer compared to post-menopausal diabetic women on a different oral hypoglycemic drug [ 296 , 297 ].…”

Section: Antidiabetic Medications As Potential Anticancer Agentsmentioning

confidence: 99%

Insulin Resistance and Cancer: In Search for a Causal Link

Chiefari

Mirabelli

Vignera

et al. 2021

IJMS

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Insulin resistance (IR) is a condition which refers to individuals whose cells and tissues become insensitive to the peptide hormone, insulin. Over the recent years, a wealth of data has made it clear that a synergistic relationship exists between IR, type 2 diabetes mellitus, and cancer. Although the underlying mechanism(s) for this association remain unclear, it is well established that hyperinsulinemia, a hallmark of IR, may play a role in tumorigenesis. On the other hand, IR is strongly associated with visceral adiposity dysfunction and systemic inflammation, two conditions which favor the establishment of a pro-tumorigenic environment. Similarly, epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNA, in IR states, have been often associated with tumorigenesis in numerous types of human cancer. In addition to these observations, it is also broadly accepted that gut microbiota may play an intriguing role in the development of IR-related diseases, including type 2 diabetes and cancer, whereas potential chemopreventive properties have been attributed to some of the most commonly used antidiabetic medications. Herein we provide a concise overview of the most recent literature in this field and discuss how different but interrelated molecular pathways may impact on tumor development.

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Section: Antidiabetic Medications As Potential Anticancer Agentsmentioning

confidence: 99%

Insulin Resistance and Cancer: In Search for a Causal Link

Chiefari

Mirabelli

Vignera

et al. 2021

IJMS

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“…Metformin, a drug used to treat type 2 diabetes, is the most widely prescribed diabetes medication worldwide and has many beneficial effects, including anticancer effects [ 14 – 16 ]. Numerous studies have claimed that metformin could suppress the growth of cancer cells in multiple types of cancer including gastroenterological, colorectal, liver, lung, breast, and pancreatic cancer [ 17 – 24 , 46 – 48 ].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies claim that metformin could suppress the growth of cancer cells in various cancers [18][19][20][21][22][23][24]. However, there was insufficient evidence based on the exact mechanisms or randomized controlled trials [25,26].…”

Section: Introductionmentioning

confidence: 99%

“…An observational study in 2005 demonstrated that metformin had an inhibitory effect on all cancer types (23% reduction in the incidence of any cancer) [ 17 ], and since then, research interest in the anticancer and therapeutic effects of metformin has increased. Numerous studies claim that metformin could suppress the growth of cancer cells in various cancers [ 18 – 24 ]. However, there is insufficient evidence based on the exact mechanisms or randomized controlled trials [ 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

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Effects of early medication treatment and metformin use for cancer prevention in diabetes patients: a nationwide sample cohort study in Korea using extended landmark time analysis

Seo

2021

Epidemiol Health

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Effects of early medication treatment and metformin use for cancer prevention in diabetes patients: a nationwide sample cohort study using extended landmark-time analysis Abstract Objectives: This study aimed to demonstrate the effectiveness of early medication treatment and metformin use for cancer prevention in type 2 diabetes patients. Methods: A population-based cohort data was used from the Korean National Health Insurance Service-National Sample Cohort database (KNHIS-NSC) for 2002-2013.Patient-specific medication prescription status was defined by the landmark-time (LMT; a fixed-time after cohort entry), considering both pre-and post-LMT prescription drugs to control methodological biases in observational study. LMT was set to 2 years.Logistic regression analysis with multivariable adjustment was conducted to analyze the cancer incidence by patient-specific medication prescription status.Results: Only 33.36% of the subjects were prescribed medication early (before LMT) with compliance. Cancer incidence with early prescription and compliance was 25% lower (OR=0.75, 95% CI=0.67-0.84) than those without, and as an early prescribing medication, metformin monotherapy and metformin combination therapy had a 34% (OR=0.66, 95% CI=0.51-0.83) and 25% (OR=0.75, 95% CI=0.64-0.88) lower cancer risk than non-users, respectively. Patients who were prescribed late (after LMT) but did not comply with the prescription had a 24% (OR=1.24, 95% CI=0.97-1.58) higher cancer incidence than non-users. Among patients started monotherapy early and unchanged through the entire follow-up, those who started on metformin had a 37% E p u ba h e a d o f p r i n t 2 (OR=0.63, 95% CI=0.41-0.99) lower risk of cancer than non-metformin.Conclusions: Doctors must prescribe antidiabetic medication early, and the patient must comply with the prescribed medication regardless of the time of prescription to prevent cancer in diabetic patients. Metformin monotherapy or combination is recommended as early prescription.

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“…Metformin is the first-line type 2 diabetes mellitus treatment that works by reducing insulin resistance and fasting plasma insulin levels, leading to a reduction in blood glucose concentrations without causing overt hypoglycemia [12]. Several observational studies have shown that metformin may also reduce cancer risk and improve the prognosis and survival of cancer patients [62][63][64]. The plausible mechanisms that explain this association focus largely on inhibiting growth stimuli and metabolic processes within cancer cells and can be divided into insulin-dependent and -independent mechanisms that alter cancer cell growth [65].…”

Section: Metforminmentioning

confidence: 99%

Type 2 Diabetes Mellitus and Cancer: Epidemiology, Physiopathology and Prevention

et al. 2021

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Individuals with type 2 diabetes mellitus are at greater risk of developing cancer and of dying from it. Both diseases are age-related, contributing to the impact of population aging on the long-term sustainability of health care systems in European Union countries. The purpose of this narrative review was to describe, from epidemiological, pathophysiological and preventive perspectives, the links between type 2 diabetes mellitus and the most prevalent cancers in these patients. Multiple metabolic abnormalities that may occur in type 2 diabetes mellitus, particularly obesity, could explain the increased cancer risk. In addition, the effectiveness of drugs commonly used to treat type 2 diabetes mellitus (e.g., metformin and thiazolidinediones) has been broadly evaluated in cancer prevention. Thus, a better understanding of the links between type 2 diabetes mellitus and cancer will help to identify the contributing factors and the pathophysiological pathways and to design personalized preventive strategies. The final goal is to facilitate healthy aging and the prevention of cancer and other diseases related with type 2 diabetes mellitus, which are among the main sources of disability and death in the European Union and worldwide.

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Metformin use reduced the overall risk of cancer in diabetic patients: A study based on the Korean NHIS-HEALS cohort

Cited by 16 publications

References 36 publications

Insulin Resistance and Cancer: In Search for a Causal Link

Insulin Resistance and Cancer: In Search for a Causal Link

Effects of early medication treatment and metformin use for cancer prevention in diabetes patients: a nationwide sample cohort study in Korea using extended landmark time analysis

Type 2 Diabetes Mellitus and Cancer: Epidemiology, Physiopathology and Prevention

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