The effects and mechanisms of metformin therapy on the mitigation of COVID-19 infection in individuals with type 2 diabetes mellitus
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Abstract
Type 2 diabetes mellitus and coronavirus disease 2019 independently are not only highly prevalent diseases with enormous impact on individual morbidity and mortality, but they pose a severe burden on the broader healthcare system as well. And when the patient suffers from both conditions, the deleterious health effects multiply manifold. For example, the systemic inflammation induced by both conditions can in combination lead to severe lung injury and endothelial damage, increased risk of cardiovascular events, immune dysfunction, and poorer glucose control; the resulting hyperglycemia can worsen the viral inflammation, and the systemic inflammation can in turn exacerbate the hyperglycemia. Fortunately for type 2 diabetes, biguanides like metformin are highly effective at lowering blood glucose levels, as shown through decades of preclinical, experimental, and observational studies. Given metformin’s well-known pleiotropic effects in protecting against aging, cancer, and cardiovascular and neurological diseases, the goal of this thesis is to assess the clinical epidemiological evidence surrounding the efficacy of metformin in mitigating COVID-19-related morbidity and mortality. The thesis then explores the specific physiological mechanisms through which metformin exerts its wide-ranging protective effects against thrombosis, cardiovascular events, pulmonary fibrosis and dysfunction as well as its anti-inflammatory and anti-viral effects. Finally, the thesis explores the drawbacks and risks of metformin, in particular investigating the impact of lactic acidosis (a well-known side effect of metformin treatment) in patients with COVID-19.