Metformin Exposure in Patients with Cirrhosis and Diabetes

Metformin exposure in patients with cirrhosis and diabetes appears to be safe and is independently associated with reduced overall, but not liver-related mortality, reduced HCC, or reduced hepatic decompensation after adjusting for multiple concomitant exposures, according to a recent study published in the Clinical Gastroenterology and Hepatology.

Type II diabetes mellitus worsens the prognosis of cirrhosis. Multiple medications including metformin and statins often are 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.

The researchers 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 of the Study

Among 74,984 patients with cirrhosis, diabetes mellitus was present before the diagnosis of cirrhosis in 53.8%, and was diagnosed during follow-up evaluation in 4.8%. Before the diagnosis of cirrhosis, 11,114 patients had active utilization of metformin. In these patients, metformin, statin, and angiotensinogen-converting enzyme inhibitor/angiotensin-2-receptor blocker exposure were associated independently with reduced mortality (metformin hazard ratio, 0.68; 95% CI, 0.61-0.75); metformin was not associated with reduced hepatocellular carcinoma or hepatic decompensation after adjustment for concomitant statin exposure. For patients with diabetes before a diagnosis of cirrhosis but no prior metformin exposure, metformin similarly was associated with reduced mortality (hazard ratio, 0.72; 95% CI, 0.35-0.97), but not with reduced hepatocellular carcinoma or hepatic decompensation.

Thus, the researchers concluded that the metformin use in patients with cirrhosis and diabetes appears safe and is associated independently with reduced overall, but not liver-related, mortality, hepatocellular carcinoma, or decompensation after adjusting for concomitant statin and angiotensinogen-converting enzyme inhibitor/angiotensin-2-receptor blocker exposure.

Reference

Effects of Metformin Exposure on Survival in a Large National Cohort of Patients With Diabetes and Cirrhosis by David E Kaplan et al. published in the Clinical Gastroenterology and Hepatology
DOI: 10.1016/j.cgh.2020.08.026