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Long‐term metformin use may improve clinical outcomes in diabetic patients with non‐alcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis
Author(s) -
VilarGomez Eduardo,
Vuppalanchi Raj,
Desai Archita P.,
Gawrieh Samer,
Ghabril Marwan,
Saxena Romil,
Cummings Oscar W.,
Chalasani Naga
Publication year - 2019
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.15331
Subject(s) - medicine , metformin , steatohepatitis , cirrhosis , hepatocellular carcinoma , diabetes mellitus , gastroenterology , type 2 diabetes , fibrosis , decompensation , fatty liver , insulin , endocrinology , disease
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.