METFORMIN USE IS ASSOCIATED WITH LESS FREQUENT SEVERE LIVER INJURY UPON HOSPITAL ADMISSIN WITH COVID-19

ABSTRACT

Introduction In a study involving > 10,000 patients hospitalized with COVID-19, we found that liver injury, which was present in ~70% of patients upon hospital admission, correlates with in-hospital mortality (Satapathy et al., Eur J Gastroenterol Hepatol 2021). Curiously, severe liver chemistry abnormalities (LCA) were seen less often in patients with diabetes or hypertension, although these diseases confer increased risk of severe disease. This raises the question whether home medications protect from COVID-19 associated liver injury. We now analyzed associations between LCA and twenty-six groups of antidiabetic, antihypertensive, and other common mediations. Results 9898 patients hospitalized with COVID-19 in 13 hospitals in New York between March 1 to August 31, 2020, who had an complete records on admission were retrospectively analyzed. LCA measured were alanine and aspartate aminotransferases, alkaline phosphatase, and bilirubin, and were defined as absent, mildmoderate (up to four times elevated), or severe. Diseases and socioeconomic factors were similar to the initial study. 67.2% had hypertension, and 40.8% had diabetes. The most common medications included insulin (12.2%), metformin (18.3%), sulfonylureas (6.8%), DDP4 inhibitors (6.3%), ACE inhibitors (14.8%), ARBs (18.6%), beta-blockers (33.2%), calcium-channel blockers (26.5%), diuretics (21.6%), statins (41.5%), PPIs (22.1%), H2- blockers (6.8%), antiplatelets (31.0%), anticoagulants (20.5%). Comparisons between groups were analyzed using Kruskal-Wallis test, chi-squared test, and Fisher's exact test. Univariate and multivariate regression analysis were performed. Univariate analysis showed a higher risk for severe LCA in men, Asian and Black race, non-Hispanic ethnicity. As in our prior analysis, hypertension and diabetes were associated with less frequent severe LCA. In addition, hyperlipidemia, CAD, CHF, atrial fibrillation, CKD, ESRD, GERD, asthma, COPD, cancer, and liver disease were inversely associated with severe LCA. Medications that were associated with less frequent severe LCA included statins, ACE, ARBs, calcium-channel blockers, betablockers, diuretics, antiplatelet medications, insulin, biguanide, sulfonylureas, PPIs, H2- blockers, and anticoagulants, but not oral steroids. In multivariate analysis, male gender, Asian and Black race were associated with increased risk of severe LCA. Hypertension, ESRD and asthma were associated with less frequent severe LCA, but not diabetes. Among medications, only metformin showed a statistically significant correlation with severe LCA on admission, with a hazard ratio 0.57 (p 0.0002). Conclusions Metformin use was inversely associated with severe liver chemistry abnormalities upon hospital admission with COVID- 19 in a large cohort of patients during the initial pandemic in New York.