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Metformin use in diabetes protective against COVID-19-related mortality

While type 2 diabetes has become a recognised risk factor for a worse prognosis in patients with COVID-19, less is known about how anti-diabetic treatments impact upon mortality.

It has become recognised that increasing age and a higher number of co-morbidities such as hypertension, obesity and diabetes are associated with higher levels of mortality among those infected with COVID-19.

Given that the prevalence of diabetes is often very high among this ethnic group, a team from the Hugh Kaul Precision Medicine Institute, University of Alabama, US, sought to determine the effects of different anti-diabetic treatments on mortality among an ethnically diverse population infected with COVID-19. The team retrospectively reviewed all electronic health records of subjects consecutively tested for COVID-19 between February and June 2020 at a single tertiary hospital in their area. In an effort to make the results more generalisable, the researchers included all patients within the five month period with the only exclusion criterion being a lack of available outcome data. The team sought to focus their attention on the diabetic treatments and in particular, insulin and metformin because these were the most commonly prescribed and there were too few patients prescribed other medicines to provide a meaningful statistical analysis. The primary outcome for the study was overall mortality and the researchers used logistic regression to explore the association between mortality and known risk factors and diabetic treatments.

There were 604 patients who tested positive for COVID-19 during the study period. The majority of those testing positive (43%) were aged 50 to 70 years and just over half (51.5%) were Black Africans, giving a highly significant odds of testing positive compared to those of white ethnicity (odds ratio, OR = 2.6 95% CI 2.19–3.10, p < 0.001). Overall mortality among those testing positive for COVID-19 was 11% and the presence of diabetes dramatically increased the risk of mortality (OR = 3.62 95% CI 2.11–6.2, p < 0.001). In fact, 67% of all deaths occurred among those with diabetes. Focusing on diabetic treatments, the researchers observed that use of metformin reduced the odds of dying by 62% (OR = 0.38 95% CI 0.17–0.87, p = 0.0221) although no such effect was seen with insulin. Moreover, after adjusting for the covariates age, race, sex, obesity and hypertension status, the odds ratio remained significant (OR = 0.33 95% CI 0.13–0.84, p = 0.0210). The researchers also observed that neither BMI or HBA1C levels were lower in those taking metformin thus discounting these as explanatory factors.

The authors noted that while the presence of type 2 diabetes was associated with an increased mortality risk in those with COVID-19 (as reported in other studies) there appeared to be a protective effect among diabetic patients treated with metformin although they were unable to explain their findings and called for more research to understand how metformin conferred these effects.

Crouse AB et al. Metformin use is associated with reduced mortality in a diverse population with COVID-19 and diabetes. Front Endocrinol 2021.