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#Diabetes and Endocrinology
Type 2 diabetes and obesity are considered important risk factors for severe Covid-19. Visceral adipocytes secrete many proinflammatory and coagulopathic molecules that are implicated in Covid-19 morbidity. These include interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and D-dimer. TNF-alpha contributes to insulin resistance, and its levels are higher in people with type 2 diabetes. Moreover, levels of anti-inflammatory cytokine, IL-10 are lower in type 2 diabetes and obesity. Metformin, a widely used drug for managing type 2 diabetes, decreases TNF-alpha and IL-6, and increases IL-10. The investigators thus conducted a retrospective cohort analysis to find out whether metformin could reduce Covid-19-related mortality and whether sex-specific interactions exist. They evaluated de-identified claims data from United Health Group (UHG)s Clinical Discovery Claims Database. Patient data were eligible for inclusion if they were aged ≥18 years, had type 2 diabetes or obesity, at least 6 months of continuous enrolment in 2019, and admission to hospital for Covid-19 confirmed by polymerase chain reaction, manual chart review by UHG, or reported from the hospital to UHG.
Out of 15,380 people with pharmacy claims data from January 1 to June 7, 2020, 6,256 were eligible for inclusion. Of these, 3,302 (52.8%) were females. In unadjusted analyses, metformin use was associated with decreased mortality. Moreover, metformin was associated with reduced mortality in women by Cox proportional hazards [hazard ratio (HR): 0.785, 95% confidence interval (CI): 0.650–0.951)] and propensity matching [odds ratio (OR): 0.759, 95% CI: 0.601–0.960, p=0.021). Apart from reducing TNF-alpha, other mechanisms that could underline the potential role of metformin in reducing the severity of Covid-19 are modulation of angiotensin-converting enzyme 2 receptor, reduction in release of inflammatory cytokine, improvement in neutrophil to lymphocyte ratio, decrease in glycemia, mast cell stabilisation, reduction in thrombosis, and improvement in endothelial function.
In this study, a link was reported between intake of metformin and reduction in mortality in women with type 2 diabetes or obesity who were admitted to hospital for Covid-19. A strong sex-specific response to metformin in Covid-19 patients indicates that TNF-reduction may be the main way by which it reduced mortality inthis patient population. However, prospective studies are required to further elucidate the underlying mechanism.
- Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis. Available at: https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(20)30033-7/fulltext Accessed on 10 Dec 2020