Metformin and risk of hepatocellular carcinoma in patients with type 2 diabetes

Tseng, Chin‐Hsiao

doi:10.1111/liv.13872

Cited by 102 publications

(76 citation statements)

References 24 publications

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“…A pivotal, population‐based cohort study including 10 309 patients with T2DM observed a significantly decreased cancer‐related mortality for metformin compared to sulphonylurea and insulin . These results have been validated in the context of HCC within several, large observational studies including up to 97 430 patients with HCC demonstrating a reduced HCC for metformin users when compared to diabetic and/or non‐diabetic controls . Finally, two meta‐analyses summarizing 10 and 13 studies reported a 50% reduction of HCC incidence among up to 481 358 participants including 240,678 patients with HCC .…”

Section: Discussionmentioning

confidence: 82%

“…40 These results have been validated in the context of HCC within several, large observational studies including up to 97 430 patients with HCC demonstrating a reduced HCC for metformin users when compared to diabetic and/or non-diabetic controls. [8][9][10]41 Finally, two meta-analyses summarizing 10 and 13 studies reported a 50% reduction of HCC incidence among up to 481 358 participants including 240,678 patients with HCC. 11,12 These convincing results have led to the acknowledgement of HCC risk reduction by metformin within the current German practice guideline.…”

Section: Discussionmentioning

confidence: 99%

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Treatment with metformin is associated with a prolonged survival in patients with hepatocellular carcinoma

Schulte

Scheiner

Voigtländer

et al. 2019

Liver International

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Background Hepatocellular carcinoma (HCC) is one of the most lethal cancers. Nutrition‐ and life style‐associated risk factors are increasingly prevalent. Metformin, the mainstay of type 2 diabetes mellitus (T2DM)‐treatment, reduces the risk of hepatocarcinogenesis. However, its influence on the prognosis of patients with HCC has not been investigated on a large scale, yet. Methods Five thousand and ninety‐three patients treated for HCC between 2000 and 2016 at three referral centres were included in this retrospective multicentre study. The aim of this study was to assess whether treatment with metformin for T2DM is associated with a prolonged overall survival (OS) in patients diagnosed with HCC. Results Among 5093 patients with HCC, 1917 patients (37.6%) were diagnosed with T2DM, of which 338 (17.6%) received treatment with metformin. Compared to diabetic patients not treated with metformin, patients on metformin had a significantly better hepatic function (Child‐Pugh‐Score A: 69.2% vs 47.4%, P < 0.001) and underwent significantly more often tumour resection (22.1% vs 16.5%, P = 0.024). Patients on metformin had a significantly longer median OS (mOS) compared to diabetic patients not treated with metformin (22 vs 15 months, P = 0.019). The prolongation of survival was most significant in patients treated with surgery. Using a propensity score match (PSM), patients were adjusted for hepatic function and initial therapy. In the matched cohorts, mOS remained significantly longer in metformin‐treated patients (22 vs 16 months, P = 0.021). Co‐treatment of metformin and sorafenib was associated with a survival disadvantage. Conclusion Treatment with metformin was associated with an improved survival in patients with T2DM and HCC. This effect was most pronounced in patients at potentially curative tumour stages.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Treatment with metformin is associated with a prolonged survival in patients with hepatocellular carcinoma

Schulte

Scheiner

Voigtländer

et al. 2019

Liver International

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“…Interestingly, one study reported a positive association only in NASH cirrhotic patients, and not in other aetiologies such as alcohol use and viral hepatitis . Metformin use has also been associated with decreased risk of cancers, including HCC in diabetic patients . A recently published meta‐analysis, including 10 studies reporting 22 650 cases of hepatocellular carcinoma in 334 307 patients with type 2 diabetes, showed a 50% reduction in hepatocellular carcinoma incidence with metformin use .…”

Section: Introductionmentioning

confidence: 99%

“…19 Metformin use has also been associated with decreased risk of cancers, including HCC in diabetic patients. [22][23][24][25] A recently published meta-analysis, including 10 studies reporting 22 650 cases of hepatocellular carcinoma in 334 307 patients with type 2 diabetes, showed a 50% reduction in hepatocellular carcinoma incidence with metformin use. 24 Another recent large, population-based, casecontrol study using the Taiwanese National Health Insurance Research Database reported that, among diabetic patients, metformin users had a 21% lower risk of hepatocellular carcinoma after adjusting by several confounders including the presence of cirrhosis and different aetiologies of chronic liver disease.…”

Section: Introductionmentioning

confidence: 99%

Long‐term metformin use may improve clinical outcomes in diabetic patients with non‐alcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis

Vilar‐Gomez

Vuppalanchi

Desai

et al. 2019

Aliment Pharmacol Ther

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Summary Background Metformin may protect against hepatocellular carcinoma and mortality among patients with type 2 diabetes. Aim To investigate whether long‐term use of metformin improves survival and reduces liver‐related outcomes among patients with type 2 diabetes and non‐alcoholic steatohepatitis. Methods A total of 191 diabetic patients with biopsy‐proven non‐alcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis were retrospectively identified at Indiana University Medical Center between October 2004 and January 2016. Of them, 110 were users and 81 never‐users of metformin. Primary outcomes were transplant‐free survival, development of hepatocellular carcinoma or a first event of hepatic decompensation. Results Cirrhosis was present in 85% of metformin users and 88% of nonusers. Metformin dose was greater than or equal to 1 g/d in 104 out of 110 users and its median duration of use was 6 (95% CI: 4.4‐7.9) years. The mean follow‐up was 6.92 and 6.80 years for metformin users and non‐users, respectively. During follow‐up, 28 patients developed hepatocellular carcinoma (metformin users: 7, nonusers: 21), and 52 died (metformin users: 7, nonusers: 24) or were transplanted (metformin users: 13, non‐users: 13). Metformin use was associated with lower risk of overall mortality or transplant (HR: 0.42; 95% CI: 0.24‐0.74, P = 0.003) and hepatocellular carcinoma (sHR: 0.25; 95% CI: 0.11‐0.58, P = 0.001), and remained independently associated with both outcomes after propensity‐score and covariate‐adjusted analyses. No instances of hepatotoxicity or lactic acidosis were observed. Conclusion Our study demonstrated an association between long‐term metformin use and reduced the risk of all‐cause mortality/transplant and hepatocellular carcinoma in diabetics with non‐alcoholic steatohepatitis and advanced fibrosis.

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“…Metformin is well known for its anti-diabetic role [26]. It was also shown that metformin reduced the risk of cancer in patients with T2DM [27,28]. The role of metformin in suppressing the proliferation of GC cells is related to its role in blocking cell cycles, which could explain why metformin decreased tumour size in mice with xenograft GC tissues [29,30].…”

Section: Discussionmentioning

confidence: 99%

Synergic effect of diabetes mellitus and H. pylori infection on proliferation of cells via downregulating the expression of PTEN by hypermethylating its promoter region

Lu¹,

Han²,

Ren³

et al. 2020

Preprint

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Metformin and risk of hepatocellular carcinoma in patients with type 2 diabetes

Abstract: Metformin was associated with a reduced risk of HCC in a dose-response pattern. Users of both metformin and aspirin or metformin and statin had the lowest risk.

Cited by 102 publications

References 24 publications

Treatment with metformin is associated with a prolonged survival in patients with hepatocellular carcinoma

Treatment with metformin is associated with a prolonged survival in patients with hepatocellular carcinoma

Long‐term metformin use may improve clinical outcomes in diabetic patients with non‐alcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis

Synergic effect of diabetes mellitus and H. pylori infection on proliferation of cells via downregulating the expression of PTEN by hypermethylating its promoter region

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