Background & aims: Type II diabetes mellitus worsens the prognosis of cirrhosis. Multiple medications including metformin and statins are often co-administered to manage patients with diabetes. The aim of this study was to assess the impact of metformin exposure on mortality, hepatic decompensation, and hepatocellular carcinoma in individuals with diabetes and cirrhosis, controlling for multiple concomitant exposures.
Methods: We performed a retrospective cohort study of patients with cirrhosis diagnosed between January 1, 2008, through June 30, 2016, in the Veterans Health administration. Marginal structural models and propensity matching approaches were implemented to quantify the treatment effect of metformin in patients with pre-existing diabetes with or without prior metformin exposure.
Results: Among 74,984 patients with cirrhosis, diabetes mellitus was present prior to the diagnosis of cirrhosis in 53.8% and was diagnosed during follow-up in 4.8%. Prior to the diagnosis of cirrhosis, 11,114 patients had active utilization of metformin. In these patients, metformin, statin, and ACEI/A2RB exposure were independently associated with reduced mortality (metformin HR 0.68 95%CI 0.61-0.75); metformin was not associated with reduced hepatocellular carcinoma (HCC) or hepatic decompensation after adjustment for concomitant statin exposure. For patients with diabetes prior to diagnosis of cirrhosis but no prior metformin exposure, metformin was similarly associated with reduced mortality (HR 0.72 95%CI 0.35-0.97) but not with reduced HCC or hepatic decompensation.
Conclusions: Metformin use in patients with cirrhosis and diabetes appears safe and is independently associated with reduced overall but not liver-related mortality, hepatocellular carcinoma or decompensation after adjusting for concomitant statin and ACEI/A2RB exposure.