Metformin Use Associated with Reduced COVID-19 Mortality in Obese, Diabetic Women

A new study funded by the National Heart, Lung, and Blood Institute suggests a common diabetes treatment was associated with significant reductions in mortality among women with obesity or type 2 diabetes admitted to the hospital coronavirus disease 2019 (COVID-19).

A retrospective cohort analysis of data from more than 15,000 patients in the UnitedHealth Group (UHG)’s Clinical Discovery Claims Database, results suggests metformin use was associated with a significant reduction in mortality in women with obesity or type 2 diabetes at admission, but investigators pointed out this effect was not present on the overall study population, which included men and women.

“In a large de-identified claims database of adults with type 2 diabetes or obesity, metformin was associated with significantly decreased mortality in women admitted to hospital with COVID-19, with no significant mortality reduction in men,” wrote investigators. “Metformin has a good safety profile, availability, and needs to be prospectively assessed in patients with COVID-19 to understand mechanism, duration, and timing of treatment necessary for benefit.”

With multiple studies outlining the effects of comorbid conditions, such as obesity and type 2 diabetes, on outcomes of patients hospitalized with COVID-19, a team from the University of Minnesota sought to assess whether metformin’s anti-inflammatory effects might impact mortality in patients. With this in mind, they designed their analysis to include patients 18 years or older with type 2 diabetes or obesity admitted to the hospital with COVID-19 in the UHG database from January 1-June 7, 2020.

The investigators initial search yielded a cohort of 15,380 patients with COVID-19 confirmed by PCR. After eliminating patients with missing data related to age and those without a history of diabetes or obesity, 6256 patients were deemed eligible for inclusion in the current analysis.

The primary outcome of the analysis was in-hospital mortality. Investigators noted those without hospital dispositions and those who remained in the hospital beyond June 7, 2020 were censored in Cox proportional hazards model analyses and excluded from mixed-model and propensity-matched analyses. Metformin use was defined as more than 90 days of claims during the year before admission to the hospital.

The median age of the overall study cohort was 73 (IQR, 58-88) years and 52.8% were women. Of the 6256 patients included in the study, 3923 reported metformin use and 2333 reported no metformin use. Overall, 16.9% of patients in the metformin group and 20.2% of patients in the non-metformin group died of COVID-19 while hospitalized.

In the investigators' analyses, metformin use was not associated with significantly reduced mortality in the overall study cohort when assessed in Cox proportional hazards stratified model (HR, 0.887; 95% CI, 0.782-1.008) or propensity matching (OR, 0.912; 95% CI, 0.777-1.071; P=.15). However, further analysis indicated metformin use was associated with decreased mortality in women by Cox proportional hazards (HR, 0.785; 95% CI, 0.65-0.951) and propensity matching (OR, 0.759; 95% CI, 0.82-1.14; P=.021).

“To our knowledge, this is the first study to report decreased mortality with outpatient metformin use in women with type 2 diabetes or obesity in a large cohort of patients admitted to hospital in the USA for COVID-19, and to describe a sex difference in this response to metformin. These findings could have wide-reaching effects, because more than 42% of women in the USA have obesity,” investigators wrote.

This study, “Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis,” was published in The Lancet Health Longevity.