Metformin use and incidence cancer risk: evidence for a selective protective effect against liver cancer

Murff, Harvey J.; Roumie, Christianne L.; Greevy, Robert A.; Hackstadt, Amber J.; McGowan, Lucy D’Agostino; Hung, Adriana M.; Grijalva, Carlos G.; Griffin, Marie R.

doi:10.1007/s10552-018-1058-4

Cited by 48 publications

(35 citation statements)

References 37 publications

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“…In contrast, sulfonylurea use (OR, 1.62; 95% CI, 1.16-2.24) and insulin use (OR, 2.61; 95% CI, 1.46-4.65) were associated with increased HCC incidence. 58 Other recent studies have further confirmed an association between metformin and decreased HCC incidence, 59,60 although uniform assessment of co-existing NASH was not performed in these studies. Metformin and other antidiabetic medications, such as sulfonylureas, insulin, sodiumglucose cotransporter-2 inhibitors, and dipeptidyl peptidase-4 inhibitors have not demonstrated meaningful improvement in liver histology end points among patients with NAFLD.…”

Section: Best Practice Advice 7: Optimal Management Of Diabetes and Dmentioning

confidence: 94%

AGA Clinical Practice Update on Screening and Surveillance for Hepatocellular Carcinoma in Patients With Nonalcoholic Fatty Liver Disease: Expert Review

et al. 2020

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Nonalcoholic fatty liver disease (NAFLD) is a leading etiology for chronic liver disease with an immense public health impact and affects >25% of the US and global population. Up to 1 in 4 NAFLD patients may have nonalcoholic steatohepatitis (NASH). NASH is associated with significant morbidity and mortality due to complications of liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). Recent data confirm that HCC represents the fifth most common cancer and is the second leading cause of cancer-related death worldwide, and NAFLD has been identified as a rapidly emerging risk factor for this malignancy. NAFLD-associated liver complications are projected to become the leading indication for liver transplantation in the next decade. Despite evidence that NAFLD-associated HCC may arise in the absence of cirrhosis, is often diagnosed at advanced stages, and is associated with lower receipt of curative therapy and with poorer survival, current society guidelines provide limited guidance/recommendations addressing HCC surveillance in patients with NAFLD outside the context of established cirrhosis. Limited data are presently available to guide clinicians with respect to which patients with NAFLD should undergo HCC surveillance, optimal screening tools, frequency of monitoring, and the influence of coexisting host-and disease-related risk factors. Herein we present an evidence-based review addressing HCC risk in patients with NAFLD and provide Best Practice Advice statements to address key issues in clinical management.

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Section: Best Practice Advice 7: Optimal Management Of Diabetes and Dmentioning

confidence: 94%

AGA Clinical Practice Update on Screening and Surveillance for Hepatocellular Carcinoma in Patients With Nonalcoholic Fatty Liver Disease: Expert Review

et al. 2020

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“… 18 Murff et al reported the strong inverse association between metformin and liver cancer, but not gastric cancer. 17 Population-based studies in the Netherlands, Sweden and Taiwan also indicated that metformin did not reduce GC risk. 14 , 21 , 23…”

Section: The Efficacy Of Metformin For Gastric Cancer In Clinical Pramentioning

confidence: 99%

<p>Preventative and Therapeutic Effects of Metformin in Gastric Cancer: A New Contribution of an Old Friend</p>

Zhang¹,

Wen²,

Zhou³

et al. 2020

CMAR

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Gastric cancer (GC) is a cancer with high prevalence, and is one of the leading causes of cancer death worldwide. Metformin is a widely used hypoglycemic agent for type-2 diabetes mellitus (T2DM). Recently, metformin has drawn increasing attention in the field of cancer research for its emerging anti-cancer roles. However, the efficacy and underlying molecular mechanisms of metformin in the prevention and treatment for GC remain controversial. This review summarized the present clinical and mechanistic studies that investigated the efficacy of metformin in GC. It was found that the majority of clinical studies affirmed protective roles of metformin in both gastric cancer risk and survival rate. In addition, metformin’s effects in the prevention and treatment for GC involve multiple pathways mainly via AMPK and IGF-1R. It was concluded that metformin presents a unique opportunity for application against GC, but further clinical and mechanistic investigations are required to solidify the roles of metformin in GC.

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“…Without specifying the histological subtypes, a limited number of studies have reported conflicting results regarding the association between metformin use and the risk of esophageal cancer (13)(14)(15)(16)23). A case-control study from Taiwan reported an increased risk (odds ratio 2.84, 95% CI 0.99-8.18) (24), while decreased risks were instead found in cohort studies from Taiwan (HR 0.49, 95% CI 0.35-0.68) (13), and the Netherlands (HR 0.90, 95% CI 0.82-0.97) (14).…”

Section: Adherence To Metformin Therapymentioning

confidence: 99%

“…A case-control study from Taiwan reported an increased risk (odds ratio 2.84, 95% CI 0.99-8.18) (24), while decreased risks were instead found in cohort studies from Taiwan (HR 0.49, 95% CI 0.35-0.68) (13), and the Netherlands (HR 0.90, 95% CI 0.82-0.97) (14). Other studies reported no association between metformin use and esophageal cancer risk (15,16,23). The major differences in the findings of the available studies could be explained by differences in the distribution of squamous cell carcinoma and adenocarcinoma (and other less common histological types of esophageal cancer), study design, study population, data collection, adjustment for confounders, exposure measurement, comparison groups, and follow-up.…”

Section: Adherence To Metformin Therapymentioning

confidence: 99%

Association Between Metformin Use and Risk of Esophageal Squamous Cell Carcinoma in a Population-Based Cohort Study

et al. 2019

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Metformin use and incidence cancer risk: evidence for a selective protective effect against liver cancer

Cited by 48 publications

References 37 publications

AGA Clinical Practice Update on Screening and Surveillance for Hepatocellular Carcinoma in Patients With Nonalcoholic Fatty Liver Disease: Expert Review

AGA Clinical Practice Update on Screening and Surveillance for Hepatocellular Carcinoma in Patients With Nonalcoholic Fatty Liver Disease: Expert Review

<p>Preventative and Therapeutic Effects of Metformin in Gastric Cancer: A New Contribution of an Old Friend</p>

Association Between Metformin Use and Risk of Esophageal Squamous Cell Carcinoma in a Population-Based Cohort Study

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