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

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Abstract

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 uses and reduced the risk of all-cause mortality/transplant and hepatocellular carcinoma in diabetics with non-alcoholic steatohepatitis and advanced fibrosis.

Original languageEnglish (US)
JournalAlimentary Pharmacology and Therapeutics
DOIs
StatePublished - Jan 1 2019

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Metformin
Fatty Liver
Fibrosis
Hepatocellular Carcinoma
Transplants
Type 2 Diabetes Mellitus
Mortality
Lactic Acidosis
Propensity Score
Survival
Liver
Biopsy

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology
  • Pharmacology (medical)

Cite this

@article{8753a5662e3c4e07b7d4ea215f50bcc0,
title = "Long-term metformin use may improve clinical outcomes in diabetic patients with non-alcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis",
abstract = "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 uses and reduced the risk of all-cause mortality/transplant and hepatocellular carcinoma in diabetics with non-alcoholic steatohepatitis and advanced fibrosis.",
author = "Eduardo Vilar-Gomez and Raj Vuppalanchi and Archita Desai and Samer Gawrieh and Marwan Ghabril and Romil Saxena and Oscar Cummings and Naga Chalasani",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/apt.15331",
language = "English (US)",
journal = "Alimentary Pharmacology and Therapeutics",
issn = "0269-2813",
publisher = "Wiley-Blackwell",

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TY - JOUR

T1 - Long-term metformin use may improve clinical outcomes in diabetic patients with non-alcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis

AU - Vilar-Gomez, Eduardo

AU - Vuppalanchi, Raj

AU - Desai, Archita

AU - Gawrieh, Samer

AU - Ghabril, Marwan

AU - Saxena, Romil

AU - Cummings, Oscar

AU - Chalasani, Naga

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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 uses and reduced the risk of all-cause mortality/transplant and hepatocellular carcinoma in diabetics with non-alcoholic steatohepatitis and advanced fibrosis.

AB - 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 uses 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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U2 - 10.1111/apt.15331

DO - 10.1111/apt.15331

M3 - Article

JO - Alimentary Pharmacology and Therapeutics

JF - Alimentary Pharmacology and Therapeutics

SN - 0269-2813

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