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.

Preadmission use of antidiabetic medications and mortality among patients with COVID-19 having type 2 diabetes: A meta-analysis

“…Ghany et al reported that individuals using metformin at a dose of ≥1000 mg/day had lower mortality than those on 500-850 mg/day [29]. Referenced to nonusers, Ong et al reported the greatest benefit on mortality with the dose from 1000 to <2000 mg/day [52]. Our findings were consistent with these studies.…”

“…A total of 3,061,584 participants were recruited from studies . Most of them were retrospective, except for two cross-sectional studies [26,52]. The antidiabetic drugs that were investigated included metformin (42 articles), SU (21), TZD (8), AGI (8), GLP-1RA (12), DPP-4i (28), SGLT-2i (13), and insulin (33) (Table 1).…”

Association of Glucose-Lowering Drugs With Outcomes in Patients With Diabetes Before Hospitalization for COVID-19

“…The evidence network comprising 8 glucose-lowering therapies is shown in Figure 2. Among these were 148 active Five studies 25,30,34,37,43 involved more than 7 treatment groups. Eighteen studies had 4 to 6 groups, 23,24,27,28,33,35,36,[39][40][41][44][45][46][47]49,50,52,53 and 5 studies had 3 groups.…”

Targeting T cell (oxidative) metabolism to improve immunity to viral infection in the context of obesity

“…Although metformin is associated with an increased risk of developing lactic acidosis during illness, several studies looked at the question of whether or not to continue metformin treatment in patients hospitalized for COVID-19 ( 55 , 66 – 68 ). One study found that the risk of lactic acidosis associated with metformin exposure was higher in patients with severe COVID-19 disease, patients with kidney impairment, and in patients taking more than 2 doses of metformin daily ( 66 ).…”

“…One study found that the risk of lactic acidosis associated with metformin exposure was higher in patients with severe COVID-19 disease, patients with kidney impairment, and in patients taking more than 2 doses of metformin daily ( 66 ). Interestingly, several studies reported that in-hospital metformin therapy may be beneficial and reduce the risk of mortality in patients hospitalized with COVID-19 ( 55 , 67 , 68 ). It is therefore reasonable to consider continuing metformin therapy during hospitalization if kidney function is carefully monitored; however, further studies are needed before making definitive recommendations.…”