Metformin is Associated with Decreased 30-Day Mortality Among Nursing Home Residents Infected with SARS-CoV2

Abstract

Objectives The COVID-19 pandemic presents an urgent need to investigate whether existing drugs can enhance or even worsen prognosis; metformin, a known mammalian target of rapamycin (m-TOR) inhibitor, has been identified as a potential agent. We sought to evaluate mortality benefit among older persons infected with SARS-CoV-2 who were taking metformin as compared to those who were not. Design Retrospective cohort study Setting and Participants: 775 nursing home residents infected with SARS-CoV-2 who resided in one of the 134 Community Living Centers (CLC) of the Veterans Health Administration (VHA) during March 1, 2020 to May 13, 2020 were included. Methods Using a window of 14 days prior to SARS-CoV-2 testing, bar coded medication administration records were examined for dispensing of medications for diabetes. The COVID-19 infected residents were divided into groups: 1) residents administered metformin alone or in combination with other medications, 2) residents who used long acting or daily insulin, 3) residents administered other diabetes medications, and 4) residents not administered diabetes medication, including non-diabetics and untreated diabetics. Proportional hazard models adjusted for demographics, hemoglobin A1c, body mass index, and renal function. Results Relative to those not receiving diabetes medications, residents taking metformin were at significantly reduced hazard of death (adjusted HR 0.48, 95%CI 0.28, 0.84) over the subsequent 30 days from COVID-19 diagnosis. There was no association with insulin (adjusted HR 0.99, 95% 0.60, 1.64) or other diabetes medications (adjusted HR 0.71, 95% CI 0.38, 1.32). Conclusions and Implications Our data suggests a reduction in 30-day mortality following SARS-CoV-2 infection in residents who were on metformin-containing diabetes regimens. These findings suggest a relative survival benefit in nursing home residents on metformin, potentially through its mTOR inhibition effects. A prospective study should investigate the therapeutic benefits of metformin among persons with COVID-19.

Automatic identification of risk factors for SARS-CoV-2 positivity and severe clinical outcomes of COVID-19 using Data Mining and Natural Language Processing

“…disease severity. This is in line with recent clinical reports that metformin treatment of diabetic COVID-19 patients resulted in a reduced mortality rate (36)(37)(38). Metformin acts by activating the AMP-activated protein kinase AMPK,(39) which then phosphorylates angiotensin-converting enzyme 2 (ACE2) causing increase in ACE2 expression (40).…”

Protecting older patients with cardiovascular diseases from COVID-19 complications using current medications

“…The associated benefits of metformin on mortality due to COVID-19 are not restricted to patients with severe disease or hospitalisation. A retrospective analysis in nursing homes demonstrated similar results, showing that residents taking metformin had a significantly reduced 30-day mortality from COVID-19 diagnosis compared to residents without antidiabetic drugs [ 110 ].…”

“…Several studies have shown that insulin therapy was linked to poor prognosis in COVID-19 [ 107 , 108 , 110 ]. However, it is important to underline that the poorer outcomes are probably due to the fact that use of insulin reflects more advanced diabetes and patients who are often older and frailer.…”

Metformin therapy and severity and mortality of SARS-CoV-2 infection: a meta-analysis

“…The included studies were conducted in Austria [14], Belgium [15], China [16][17][18][19][20][21][22][23][24], France [25][26][27], Hong Kong [28], Iraq [29], Italy [30,31], Russia [32]which determines the high relevance of risk factor analysis for outcomes in DM patients to substantiate the strategy for this category of patients. AIM: To assess the effect of clinical and demographic parameters (age, gender, body mass index (BMI, South Korea [33,34], Spain [35,36], UK [37][38][39][40][41] and USA [42][43][44][45].…”