Metformin Use and the Risk of Cancer in Patients with Diabetes: A Nationwide Sample Cohort Study

Oh, Tak Kyu; Song, In Ae

doi:10.1158/1940-6207.capr-19-0427

Cited by 19 publications

(32 citation statements)

References 31 publications

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“… 82 Seven years later, Oh TK and Song IA conducted a nationwide sample cohort study to analyze the relationship of metformin use and cancer in diabetes patients. 83 The authors found a lack of an association between metformin treatment and the risk of cancer among diabetic patients, even in the high daily dosage groups (>1 g/day). 83 However, there might be some confounders or time bias in this study.…”

Section: Effect Of Metformin On Malignant Tumorsmentioning

confidence: 98%

“… 83 The authors found a lack of an association between metformin treatment and the risk of cancer among diabetic patients, even in the high daily dosage groups (>1 g/day). 83 However, there might be some confounders or time bias in this study. Thus, further prospective, large population-based cohort studies are needed to confirm these findings.…”

Section: Effect Of Metformin On Malignant Tumorsmentioning

confidence: 98%

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Metformin and Malignant Tumors: Not Over the Hill

Leng¹,

Jiang²,

Chen³

et al. 2021

DMSO

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Malignant tumors are a major cause of death, and their incidence is increasing worldwide. Although the survival rate for some cancers has improved, treatments for other malignant tumors are limited, and their mortality rate continues to increase. People with type 2 diabetes have a higher risk of malignant tumors and a higher mortality rate than those without diabetes. Metformin is a commonly used hypoglycemic drug. In recent years, a growing number of studies have indicated that metformin has antitumor effects and increases the sensitivity of malignant tumors to chemotherapy. However, the effect of metformin on different tumors is currently controversial, and the mechanism of metformin’s antitumor action is not fully understood. Insights into the effect of metformin on malignant tumors and the possible mechanism may contribute to the development of antitumor drugs.

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Section: Effect Of Metformin On Malignant Tumorsmentioning

confidence: 98%

Section: Effect Of Metformin On Malignant Tumorsmentioning

confidence: 98%

Metformin and Malignant Tumors: Not Over the Hill

Leng¹,

Jiang²,

Chen³

et al. 2021

DMSO

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Section: Metformin and Cancermentioning

confidence: 99%

“…In this line, Oh et al, conducted a study to investigate the association of metformin therapy with the development of cancer [80]. A total of 66,627 adult subjects with type II diabetes were included in the analysis; 29,974 were metformin users and 36,653 were controls [80]. After multivariable adjustment, the risk for the development of cancer among metformin users was not significantly different from that among controls (HR = 0.96; 95% confidence interval, 0.89-1.03; p = 0.250), suggesting a lack of association between metformin therapy and the risk of cancer among patients with diabetes [80].…”

Section: Metformin and Cancermentioning

confidence: 99%

“…A total of 66,627 adult subjects with type II diabetes were included in the analysis; 29,974 were metformin users and 36,653 were controls [ 80 ]. After multivariable adjustment, the risk for the development of cancer among metformin users was not significantly different from that among controls (HR = 0.96; 95% confidence interval, 0.89–1.03; p = 0.250), suggesting a lack of association between metformin therapy and the risk of cancer among patients with diabetes [ 80 ]. Feng et al, conducted a meta-analysis of cohort studies to evaluate a potential association of metformin use with prostate cancer risk [ 81 ].…”

Section: Antidiabetic Drugs In Cancermentioning

confidence: 99%

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Cancer Biology and Prevention in Diabetes

Srivastava

Goodwin

2020

Cells

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The available evidence suggests a complex relationship between diabetes and cancer. Epidemiological data suggest a positive correlation, however, in certain types of cancer, a more complex picture emerges, such as in some site-specific cancers being specific to type I diabetes but not to type II diabetes. Reports share common and differential mechanisms which affect the relationship between diabetes and cancer. We discuss the use of antidiabetic drugs in a wide range of cancer therapy and cancer therapeutics in the development of hyperglycemia, especially antineoplastic drugs which often induce hyperglycemia by targeting insulin/IGF-1 signaling. Similarly, dipeptidyl peptidase 4 (DPP-4), a well-known target in type II diabetes mellitus, has differential effects on cancer types. Past studies suggest a protective role of DPP-4 inhibitors, but recent studies show that DPP-4 inhibition induces cancer metastasis. Moreover, molecular pathological mechanisms of cancer in diabetes are currently largely unclear. The cancer-causing mechanisms in diabetes have been shown to be complex, including excessive ROS-formation, destruction of essential biomolecules, chronic inflammation, and impaired healing phenomena, collectively leading to carcinogenesis in diabetic conditions. Diabetes-associated epithelial-to-mesenchymal transition (EMT) and endothelial-to-mesenchymal transition (EndMT) contribute to cancer-associated fibroblast (CAF) formation in tumors, allowing the epithelium and endothelium to enable tumor cell extravasation. In this review, we discuss the risk of cancer associated with anti-diabetic therapies, including DPP-4 inhibitors and SGLT2 inhibitors, and the role of catechol-o-methyltransferase (COMT), AMPK, and cell-specific glucocorticoid receptors in cancer biology. We explore possible mechanistic links between diabetes and cancer biology and discuss new therapeutic approaches.

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Effect of diabetes medications and glycemic control on risk of hepatocellular cancer in patients with nonalcoholic fatty liver disease

et al. 2021

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Background and Aims In patients with NAFLD, those with type 2 diabetes mellitus (DM) have a high risk of progression to HCC. However, the determinants of HCC risk in these patients remain unclear. Approach and Results We assembled a retrospective cohort of patients with NAFLD and DM diagnosed at 130 facilities in the Veterans Administration between 1/1/2004 and 12/31/2008. We followed patients from the date of NAFLD diagnosis to HCC, death, or 12/31/2018. We used landmark Cox proportional hazards models to determine the effects of anti‐DM medications (metformin, insulin, sulfonylureas) and glycemic control (percent of follow‐up time with hemoglobin A1c < 7%) on the risk of HCC while adjusting for demographics and other metabolic traits (hypertension, obesity, dyslipidemia). We identified 85,963 patients with NAFLD and DM. In total, 524 patients developed HCC during a mean of 10.3 years of follow‐up. Most common treatments were metformin monotherapy (19.7%), metformin‐sulfonylureas (19.6%), insulin (9.3%), and sulfonylureas monotherapy (13.6%). Compared with no medication, metformin was associated with 20% lower risk of HCC (HR, 0.80; 95% CI, 0.93–0.98). Insulin had no effect on HCC risk (HR, 1.02; 95% CI, 0.85–1.22; p = 0.85). Insulin in combination with other oral medications was associated with a 1.6 to 1.7‐fold higher risk of HCC. Adequate glycemic control was associated with a 31% lower risk of HCC (HR, 0.69; 95% CI, 0.62–0.78). Conclusions In this large cohort of patients with NAFLD and DM, use of metformin was associated with a reduced risk of HCC, whereas use of combination therapy was associated with increased risk. Glycemic control can serve as a biomarker for HCC risk stratification in patients with NAFLD and diabetes.

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Metformin Use and the Risk of Cancer in Patients with Diabetes: A Nationwide Sample Cohort Study

Cited by 19 publications

References 31 publications

Metformin and Malignant Tumors: Not Over the Hill

Metformin and Malignant Tumors: Not Over the Hill

Cancer Biology and Prevention in Diabetes

Effect of diabetes medications and glycemic control on risk of hepatocellular cancer in patients with nonalcoholic fatty liver disease

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