Metformin for Liver Cancer Prevention in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

Zhang, Zhijiang; Zheng, Zhijie; Shi, Rong; Su, Qing; Jiang, Qingwu; Kip, Kevin E.

doi:10.1210/jc.2012-1267

Cited by 215 publications

(137 citation statements)

References 41 publications

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“…Twelve of these articles also included meta-analysis of observational studies [4, 5, 10, 12, 18-21, 27, 49, 55, 62]. Another 14 articles on meta-analyses of observational studies were also identified [63][64][65][66][67][68][69][70][71][72][73][74][75][76] ( Table 1). The meta-analyses addressed diverse medications including antidiabetics, antihyperlipidemics, antihypertensives, antirheumatics, drugs for osteoporosis, and drugs for other conditions.…”

Section: Discussionmentioning

confidence: 99%

Potential increased risk of cancer from commonly used medications: an umbrella review of meta-analyses

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Potential increased risk of cancer from commonly used medications: an umbrella review of meta-analyses

et al. 2014

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“…The effect of metformin on liver fat is weak, because of its inability to restore serum adiponectin levels in the short-term [127]. Some preclinical data support an anti-tumorigenic activity of metformin on liver cancer [128], while the demonstration of reduced rates of HCC in humans is limited to retrospective studies [129] and insufficient for evidencebased recommendations. Thiazolidinediones are peroxisome proliferator-activated receptor (PPAR)γ agonists with insulin-sensitising effects.…”

Section: Insulin Sensitisersmentioning

confidence: 99%

EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease

2016

Diabetologia

535

248

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“…The effect of metformin on liver fat is weak, because of its inability to restore serum adiponectin levels in the short-term [127] . Some preclinical data support an anti-tumorigenic activity of metformin on liver cancer [128] , while the demonstration of reduced rates of HCC in humans is limited to retrospective studies [129] and insufficient for evidence-based recommendations.Thiazolidinediones are peroxisome proliferator-activated receptor gamma (PPARγ) agonists with insulin-sensitising effects. The PIVENS trial compared low dose pioglitazone vs. vitamin E vs. placebo for 2 years in patients without overt diabetes.…”

mentioning

confidence: 99%

EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease

2016

Journal of Hepatology

3,489

1,817

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DefinitionNAFLD is characterised by excessive hepatic fat accumulation, associated with insulin resistance (IR), and defined by the presence of steatosis in >5% of hepatocytes according to histological analysis or by the proton density fat fraction (PDFF, providing a rough estimation of the volume fraction of fatty material in the liver) >5.6% assessed by proton magnetic resonance spectroscopy ( 1 H-MRS) or quantitative fat/water selective magnetic resonance imaging (MRI). NAFLD includes two pathologically distinct conditions with different prognoses: nonalcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH); the latter covers a wide spectrum of disease severity, including fibrosis, cirrhosis and hepatocellular carcinoma (HCC) ( table 2 ).The diagnosis of NAFLD requires exclusion of both secondary causes and a daily alcohol consumption ≥ 30 g for men and 20 g for women [1] . The relationship between alcohol and liver injury depends on several cofactors (type of alcoholic beverage, drinking patterns, duration of exposure, individual/genetic susceptibility), rendering simple quantitative thresholds at least partly arbitrary. Specifically, patients consuming moderate amounts of alcohol may be still predisposed to NAFLD if they have metabolic risk factors. Of note, the overall impact of metabolic risk factors on the occurrence of steatosis appears to be higher than that of alcohol in these patients [3] . The definitive diagnosis of NASH requires a liver biopsy. Recommendations• Patients with IR and/or metabolic risk factors (i.e., obesity or metabolic syndrome (MetS)) should undergo diagnostic procedures for the diagnosis of NAFLD, which relies on the demonstration of excessive liver fat (A1) • Individuals with steatosis should be screened for secondary causes of NAFLD, including a careful assessment of alcohol intake. The interaction between moderate amounts of alcohol and metabolic factors in fatty liver should always be considered (A1) • Other chronic liver diseases, that may coexist with NAFLD, should be identified as this might result in more severe liver injury (B1) Prevalence and IncidenceNAFLD is the most common liver disorder in Western countries, affecting 17-46% of adults, with differences according to the diagnostic method, age, sex and ethnicity [4] . It parallels the prevalence of MetS and its components, which also increases the risk of more advanced disease, both in adults and in children. NAFLD is also present in 7% of normalweight (lean) persons [5] , more frequently in females, at a younger age and with normal liver enzymes. Their liver disease may nonetheless be progressive [6] .NAFLD incidence has rarely been measured. It was 20-86/1,000 person-years based on elevated liver enzymes and/or on ultrasound (US), and 34/1,000 per year by 1 H-MRS [7] . The need for NAFLD screening in the community has been questioned given the high direct and indirect costs of testing, the low predictive value of non-invasive tests, the risks of liver biopsy and the lack of effective treatments [8] . Ho...

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Metformin for Liver Cancer Prevention in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

Abstract: Metformin appears to be associated with a lower risk of liver cancer in patients with type 2 diabetes. Further investigation, including mechanistic studies, well-designed cohort studies, and possibly controlled trials, is needed.

Cited by 215 publications

References 41 publications

Potential increased risk of cancer from commonly used medications: an umbrella review of meta-analyses

Potential increased risk of cancer from commonly used medications: an umbrella review of meta-analyses

EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease

EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease

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