Association Between Metformin Use and Mortality among Patients with Type 2 Diabetes Mellitus Hospitalized for COVID-19 Infection

Abstract

Introduction: Metformin has known mechanistic benefits on COVID-19 infection due to its anti-inflammatory effects and its action on the ACE2 receptor. However, some physicians are reluctant to use it in hypoxemic patients due to potential lactic acidosis. The primary purpose of the study was to determine whether metformin use is associated with survival. We also wanted to determine whether there is a difference in outcomes in subcategories of metformin use, whether at home, in-hospital, or mixed home/in-hospital use.

Objectives: This study aimed to determine an association between metformin use and mortality among patients with type 2 diabetes mellitus hospitalized for COVID-19 infection.

Methodology: This was a cross-sectional analysis of data acquired from the COVID-19 database of two tertiary hospitals in Cebu from March 1, 2020, to September 30, 2020. Hospitalized adult Filipino patients with type 2 diabetes mellitus who tested positive for COVID-19 via RT-PCR were included and categorized as either metformin users or metformin non-users.

Results: We included 355 patients with type 2 diabetes mellitus in the study, 186 (52.4%) were metformin users. They were further categorized into home metformin users (n=109, 30.7%), in-hospital metformin users (n=40, 11.3%), and mixed home/in-hospital metformin users (n=37, 10.4%). Metformin use was associated with a lower risk for mortality compared to non-users (p=0.001; OR=0.424). In-hospital and mixed home/in-hospital metformin users were associated with lower mortality odds than non-users (p=0.002; OR=0.103 and p=0.005; OR 0.173, respectively). The lower risk for mortality was noted in metformin, regardless of dosage, from 500 mg to 2 g daily (p=0.002). Daily dose between ≥1000 mg to <2000 mg was associated with the greatest benefit on mortality (p≤0.001; OR=0.252). The survival distributions between metformin users and non-users were statistically different, showing inequality in survival (χ2=5.67, p=0.017).

Conclusion: Metformin was associated with a lower risk for mortality in persons with type 2 diabetes mellitus hospitalized for COVID-19 disease compared to non-users. Use of metformin in-hospital, and mixed home/in-hospital metformin use, was also associated with decreased risk for mortality. The greatest benefit seen was in those taking a daily dose of ≥1000 mg to <2000 mg.

Keywords: COVID-19; diabetes mellitus; metformin; mortality.