Metformin Is Associated with Higher Incidence of Acidosis, but Not Mortality, in Individuals with COVID-19 and Pre-existing Type 2 Diabetes

Abstract

Summary The safety and efficacy of anti-diabetic drugs are critical for maximizing the beneficial impacts of well-controlled blood glucose on the prognosis of individuals with COVID-19 and pre-existing type 2 diabetes (T2D). Metformin is the most commonly prescribed first-line medication for T2D, but its impact on the outcomes of individuals with COVID-19 and T2D remains to be clarified. Our current retrospective study in a cohort of 1,213 hospitalized individuals with COVID-19 and pre-existing T2D indicated that metformin use was significantly associated with a higher incidence of acidosis, particularly in cases with severe COVID-19, but not with 28-day COVID-19-related mortality. Furthermore, metformin use was significantly associated with reduced heart failure and inflammation. Our findings provide clinical evidence in support of continuing metformin treatment in individuals with COVID-19 and pre-existing T2D, but acidosis and kidney function should be carefully monitored in individuals with severe COVID-19.

Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19

“…In contrast, some studies did not report such an association between metformin treatment and improved COVID-related outcomes in patients with type 2 diabetes. One retrospective observational study form China including 1213 patients with T2D hospitalised for COVID-19 (678 metformin users) found a neutral effect of metformin on 28-day mortality [32] . Another retrospective study from Korea, which was based on claims data, found no definite association between metformin use and COVID-19 outcomes [33] .…”

Development and validation of a risk score using complete blood count to predict in-hospital mortality in COVID-19 patients

“…A part of the baseline data in this manuscript have been used in our previous articles. 30 , 31 , 32 , 33 …”

Diabetes, obesity, metabolism, and SARS-CoV-2 infection: the end of the beginning

“…Although the analysis excluded individuals with contraindications for taking metformin, metabolic acidosis, including lactic acidosis, was more common in metformin-treated subjects, notably in people with clinically severe COVID-19 illness. Acidosis was more common in subjects with hypoxemia, higher metformin doses (2–3 g daily), and an estimated glomerular filtration rate (eGFR) < 60 ( Cheng et al., 2020 ); however, all-cause mortality determined at day 28 of hospitalization was not different between groups.…”

“…Cheng and colleagues retrospectively analyzed outcomes in 678 metformin- versus 535 non-metformin-treated Chinese subjects, selected from among 2,563 people hospitalized with pre-existing T2D and COVID-19, after excluding 1,350 people from the analysis, for reasons including the exclusive use of insulin or no record of using glucose-lowering medications ( Cheng et al., 2020 ). Although the analysis excluded individuals with contraindications for taking metformin, metabolic acidosis, including lactic acidosis, was more common in metformin-treated subjects, notably in people with clinically severe COVID-19 illness.…”