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 W.
AU - Chalasani, Naga
N1 - Funding Information:
Funding information Declaration of personal interests: Naga Chalasani has served as speaker, consultant or an advisory board member for NuSirt, Abbvie, Eli Lilly, Afimmune (DS Biopharma), Allergan (Tobira), Madrigal, Shire, Axovant, Coherus, Pronova (BASF), and Genentech. He also has received research funding from Intercept, Lilly, Galectin Therapeutics and Cumberland. Samer Gawrieh has served as consultant for TransMedics and received research funding from Cirius, Galmed and Zydus. Oscar W Cummings has served as consultant for Novo-Nordisk. Marwan Ghabril has received research funding from Conatus and Valeant. Raj Vuppalanchi has received research funding from Gilead, Zydus, and Intercept. He also has served as consultant for Enanta. Romil Saxena has served as consultant for Targos Molecular Pathology, Arrowhead Pharmaceuticals and Lilly & Co. Archita Desai and Eduardo Vilar-Gomez disclose no outside interests. Declaration of funding interests: There was no external funding for this study. No writing support was provided.
Funding Information:
Declaration of personal interests: Naga Chalasani has served as speaker, consultant or an advisory board member for NuSirt, Abbvie, Eli Lilly, Afimmune (DS Biopharma), Allergan (Tobira), Madrigal, Shire, Axovant, Coherus, Pronova (BASF), and Genentech. He also has received research funding from Intercept, Lilly, Galectin Therapeutics and Cumberland. Samer Gawrieh has served as consultant for TransMedics and received research funding from Cirius, Galmed and Zydus. Oscar W Cummings has served as consultant for Novo‐Nordisk. Marwan Ghabril has received research funding from Conatus and Valeant. Raj Vuppalanchi has received research funding from Gilead, Zydus, and Intercept. He also has served as consultant for Enanta. Romil Saxena has served as consultant for Targos Molecular Pathology, Arrowhead Pharmaceuticals and Lilly & Co. Archita Desai and Eduardo Vilar‐Gomez disclose no outside interests.
Publisher Copyright:
© 2019 John Wiley & Sons Ltd
PY - 2019/8
Y1 - 2019/8
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 use 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 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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U2 - 10.1111/apt.15331
DO - 10.1111/apt.15331
M3 - Article
C2 - 31157422
AN - SCOPUS:85067080846
SN - 0269-2813
VL - 50
SP - 317
EP - 328
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
IS - 3
ER -