Metformin usage and the risk of colorectal cancer: a national cohort study

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

doi:10.1007/s00384-020-03765-x

Cited by 16 publications

(9 citation statements)

References 33 publications

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“…Although the cancer-preventive effects of metformin remain controversial, its usage and subsequent reduction of cancer risk has been seen in certain cancer patients, particularly those subjects possessing a diabetic background [ 13 , 15 , 37 , 38 ]. To simulate clinical situations involving metformin prescription and use, experimental models of tumor growth in rodents have yielded promising evidence showcasing the anticancer potential of metformin [ 27 , 28 , 29 , 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…Algire et al [ 27 ] found that metformin had an inhibitory effect on tumor growth in C57BL/6 mice fed with HFD, while a limited effect was observed in C57BL/6 mice fed with a normal control diet. Although metformin use and its ability to reduce cancer risk are found in cancer patients [ 13 , 15 , 37 , 38 ], the aforementioned controversy indicates that metformin may only offer benefits to certain cancer populations with remarkable metabolic abnormalities.…”

Section: Discussionmentioning

confidence: 99%

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Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing Mice

Chen

Chang

et al. 2022

IJMS

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Metformin may offer benefits to certain cancer populations experiencing metabolic abnormalities. To extend the anticancer studies of metformin, a tumor model was established through the implantation of murine Lewis Lung Carcinoma (LLC) cells to Normal Diet (ND)-fed and High-Fat Diet (HFD)-fed C57BL/6 mice. The HFD-fed mice displayed metabolic and pro-inflammatory alterations together with accompanying aggressive tumor growth. Metformin mitigated tumor growth in HFD-fed mice, paralleled by reductions in circulating glucose, insulin, soluble P-selectin, TGF-β1 and High Mobility Group Box-1 (HMGB1), as well as tumor expression of cell proliferation, aerobic glycolysis, glutaminolysis, platelets and neutrophils molecules. The suppressive effects of metformin on cell proliferation, migration and oncogenic signaling molecules were confirmed in cell study. Moreover, tumor-bearing HFD-fed mice had higher contents of circulating and tumor immunopositivity of Neutrophil Extracellular Traps (NETs)-associated molecules, with a suppressive effect from metformin. Data taken from neutrophil studies confirmed the inhibitory effect that metformin has on NET formation induced by HMGB1. Furthermore, HMGB1 was identified as a promoting molecule to boost the transition process towards NETs. The current study shows that metabolic, pro-inflammatory and NET alterations appear to play roles in the obesity-driven aggressiveness of cancer, while also representing candidate targets for anticancer potential of metformin.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing Mice

Chen

Chang

et al. 2022

IJMS

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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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“…Supplemental digital content 1, http://links.lww.com/ACD/ A419 showed study characteristics. Eight case-control studies [11][12][13][14][15][16][17][18] (including 22050 CRC patients and 48 4594 controls), 19 cohort studies [9,10,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] (including 43 7688 metformin users and 118 3331 no-metformin users) and 1 randomized controlled trial (RCT) (including 71 metformin users and 62 no-metformin users) detected the effect of metformin use on the risk of CRC in DM. Additionally, 2 case-control studies [36,37] (including 400 CRC patients and 345 controls) and 6 cohort studies [38][39][40][41][42][43] (including 3938 metformin users and 3338 no-metformin users) detected the effect of metformin use on all-cause mortality of CRC in DM.…”

Section: Study Characteristicsmentioning

confidence: 99%

Effect of metformin use on the risk and prognosis of colorectal cancer in diabetes mellitus: a meta-analysis

Wang

Shi

2021

Anti-Cancer Drugs

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Whether metformin is a protective factor of colorectal cancer (CRC) among CRC patients is still not entirely clear. Thus, we conducted this systemic review and metaanalysis to provide a comprehensive review of associations between metformin therapy and CRC risk or survival outcomes for clinical decisions. Articles published before July 2021 were searched in databases (PubMed and Web of Science). Odds ratio (OR)/risk ratio (RR) or hazard ratio (HR) and their confidence intervals (CIs) were computed using STATA 12.0 software. Q test and I 2 were conducted to explore heterogeneities between studies. The present meta-analysis showed that metformin use was associated with decreased risk and lower all-cause mortality of CRC in diabetes mellitus (DM) with random-effects models (risk: OR/RR = 0.71, 95% CI, 0.64-0.80, I 2 = 89.3%, P < 0.001; allcause mortality: HR = 0.72, 95% CI, 0.62-0.83, I 2 = 60.1%, P = 0.014). In addition, the study showed that metformin use was associated with a lower CRC-specific mortality in DM in cohort studies with a fixed-effects model (HR = 0.80, 95% CI, 0.70-0.92, I 2 = 34.7%, P = 0.190). Overall, in this meta-analysis, we found that metformin may be a protective factor for CRC risk and prognosis in patients with DM. Further well-designed, large-scale clinical studies are needed to evaluate the accuracy of our findings and more preclinical experiments are needed to reveal the underlying mechanism of metformin.

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Metformin usage and the risk of colorectal cancer: a national cohort study

Cited by 16 publications

References 33 publications

Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing Mice

Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing Mice

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

Effect of metformin use on the risk and prognosis of colorectal cancer in diabetes mellitus: a meta-analysis

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