Impact of metformin use on risk and mortality of hepatocellular carcinoma in diabetes mellitus

Li, Qiaomei; Xu, Hairong; Sui, Chengjun; Zhang, Hongjuan

doi:10.1016/j.clinre.2021.101781

Cited by 19 publications

(21 citation statements)

References 45 publications

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“…[ 31 ] These findings were recently confirmed in a study showing that metformin use was associated with a significantly decreased risk of HCC in T2DM (OR 0.59, 95% CI 0.51–0.68, p < 0.001). [ 34 ] Additionally, this study indicated that metformin use was associated with a decreased all‐cause mortality in diabetic patients with HCC (HR 0.74, 95% CI 0.66–0.83, p = 0.037). [ 34 ] This finding is in accordance with those from a previous report showing a reduced overall mortality risk among metformin users (HR 0.68, 95% CI 0.61–0.75).…”

Section: T2dm Medications and Hccmentioning

confidence: 83%

“…[ 30 ] Since that time, several studies have demonstrated its potential preventative role against HCC development. [ 31 , 32 , 33 , 34 ] As an example, a metanalysis by Zhang et al including three cohort studies and four case‐control studies with more than 16,000 diabetic subjects, showed that metformin treatment was associated with a 76% reduced risk of HCC (relative risk [RR] 0.24, 95% CI 0.13–0.46, p < 0.001). [ 32 ] Importantly, the protective effect of metformin remained significant after adjusting for other risk factors such as the etiology of liver disease.…”

Section: T2dm Medications and Hccmentioning

confidence: 99%

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Diabetes medications and risk of HCC

et al. 2022

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Type 2 diabetes mellitus is a recognized risk factor for HCC in patients with liver disease, independent from the etiology of their liver disease. Hence, prevention and treatment of type 2 diabetes mellitus and its underlying cause, insulin resistance, should be considered a treatment target for patients with liver disease. The drug armamentarium for diabetes is wide and consists of agents with insulin‐sensitizing activity, agents that stimulate insulin secretion, insulin itself, and agents that reduce gastrointestinal and urinary glucose absorption. From an endocrinology perspective, the main goal of treatment is the achievement of euglycemia; however, in patients at risk of, or with known underlying liver disease, the choice of diabetic medication as it relates to potential hepatic carcinogenesis remains complex and should be carefully considered. In the last decade, increasing evidence has suggested that metformin may reduce the risk of HCC, whereas evidence for other classes of diabetic medications, particularly some of the newer agents including the sodium glucose cotransporter‐2 inhibitors and glucagon‐like peptide‐1 receptor agonists, is fewer and often inconsistent. In this review, we aim to summarize the current evidence on the potential effects of the most widely used diabetic agents on liver cancer tumorigenesis.

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Section: T2dm Medications and Hccmentioning

confidence: 83%

Section: T2dm Medications and Hccmentioning

confidence: 99%

Diabetes medications and risk of HCC

et al. 2022

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“…Our findings are consistent with the previous studies. There are studies also shown the use of metformin in DM patients is significantly associated with reduced risk and all-cause mortality of HCC (28). In human primary hepatocytes, metformin treatment inhibited M inhibited mammalian target of rapamycin (mTOR) and phosphatase and tensin homolog (PTEN), but up-regulated p62, light chain 3B II (LC3BII) and Caspase 3.…”

Section: Discussionmentioning

confidence: 99%

Dipeptidyl Peptidase 4 Inhibitors Decrease the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis C Infection and Type 2 Diabetes Mellitus: A Nationwide Study in Taiwan

Hsu

Sue

Liang

et al. 2021

Front. Public Health

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Introduction: Dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors) are incretin-based oral antidiabetic drugs. Previous studies have shown an association between increased plasma activity of DPP-4 and chronic hepatitis C virus (HCV) infection. Dipeptidyl peptidase 4 inhibitors may be associated with preventing the development of chronic HCV infection. The aim of this study was to investigate whether the use of DPP-4 inhibitors is associated with a decreased risk of hepatocellular carcinoma (HCC) in patients with diabetes mellitus (DM) and chronic HCV infection.Methods: In this retrospective cohort study, we enrolled patients with type 2 diabetes and chronic HCV infection from the National Health Insurance Research Database (NHIRD) in Taiwan. The patients were divided into two groups (DPP-4 inhibitor cohort and non-DPP-4 inhibitor cohort) according to whether or not they received DPP-4 inhibitor treatment.Results: Multivariate Cox proportional hazard regression analysis showed a significantly lower risk of HCC in the patients who took DPP-4 inhibitors compared to those who did not. Kaplan-Meier survival analysis demonstrated a significantly higher HCC-free rate in the DPP-4 inhibitor cohort than in the non-DPP-4 inhibitor cohort.Conclusion: The use of DPP-4 inhibitors was associated with a lower risk of HCC in patients with type 2 DM and chronic HCV infection.

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“…A meta-analysis showed that metformin use was associated with lower HCC incidence (odds ratio [OR], 0.59; 95% CI, 0.51–0.68) and all-cause mortality (HR, 0.74; 95% CI, 0.66–0.83) in diabetic subjects. 52 In 85,963 patients with NAFLD and diabetes at Veterans Administration hospitals, metformin use was associated with lower HCC risk (HR, 0.80; 95% CI, 0.93–0.98), which was enhanced when adequate glycemic control was achieved (HR, 0.69; 95% CI, 0.62–0.78). 53 Another meta-analysis reported that thiazolidinedione use was associated with moderately reduced HCC risk in Asian (aOR, 0.90; 95% CI, 0.83–0.97) but not in Western (aOR, 0.95; 95% CI, 0.87–1.04) subjects.…”

Section: Potential Hcc Chemoprevention Therapies With Generic Agentsmentioning

confidence: 99%

Hepatocellular Carcinoma Chemoprevention with Generic Agents

et al. 2022

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Liver cancer, mainly hepatocellular carcinoma (HCC), remains a major cause of cancer-related death worldwide. With the global epidemic of obesity, the major HCC etiologies have been dynamically shifting from viral to metabolic liver diseases. This change has made HCC prevention difficult with increasingly elusive at-risk populations as rational target for preventive interventions. Besides ongoing efforts to reduce obesity and metabolic disorders, chemoprevention in patients who already have metabolic liver diseases will have a significant impact on the poor HCC prognosis. Hepatitis B- and C-related HCC incidences have been substantially reduced by the new anti-virals, but HCC risk can persist over a decade even after successful viral treatment, highlighting the need for HCC-preventive measures also in these patients. Experimental and retrospective studies have suggested potential utility of generic agents such as lipophilic statins and aspirin for HCC chemoprevention given their well characterized safety profile, although anticipated efficacy may be modest. In this review, we overview recent clinical and translational studies of generic agents in the context of HCC chemoprevention under the contemporary HCC etiologies. We also discuss newly emerging approaches to overcome the challenges in clinical testing of the agents to facilitate their clinical translation.

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Impact of metformin use on risk and mortality of hepatocellular carcinoma in diabetes mellitus

Cited by 19 publications

References 45 publications

Diabetes medications and risk of HCC

Diabetes medications and risk of HCC

Dipeptidyl Peptidase 4 Inhibitors Decrease the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis C Infection and Type 2 Diabetes Mellitus: A Nationwide Study in Taiwan

Hepatocellular Carcinoma Chemoprevention with Generic Agents

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