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 (CLCs) 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 4 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 individuals without diabetes and patients with untreated diabetes. 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 hazard ratio (HR) 0.48, 95% confidence interval (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% CI 0.60, 1.64) or other diabetes medications (adjusted HR 0.71, 95% CI 0.38, 1.32).

Conclusions and implications: Our data suggest 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.

Keywords: COVID-19; Nursing home; diabetes; metformin.

Fig. 1

Survival curve by diabetes medication use. Shown is the survival curve in the 30-days post-testing in SARS-CoV2–positive diabetic patients on metformin (gray), insulin (violet), other diabetes drugs (light blue), and no therapy (navy). After adjustment for demographics, diabetes, obesity, renal function, and psychosis, metformin was associated with a 52% reduced hazard of mortality (adjusted hazard ratio 0.48, 95% confidence interval 0.28, 0.84).