Antidiabetic Drug Efficacy in Reduction of Mortality during the COVID-19 Pandemic

Abstract

Diabetes is a leading risk factor for a severe COVID-19 infection course, among other risk factors such as age >65 years old, chronic pulmonary disease, male sex, cancer, smoking history, cardiovascular disease, and unvaccinated patients. Anti-diabetic drugs have been proposed to treat diabetic patients with a COVID-19 infection because of their variable effects on the cellular and molecular levels. First, their ability to decrease cytokine production reduces cytokine levels in vascular cells, preventing endothelial injury and reducing the risk of thromboembolism and microvascular damage. This ability also alleviates the cytokine storm and, thus, decreases lung injury which is the hallmark of a severe COVID-19 infection. Additionally, by decreasing gut inflammation, anti-diabetic drugs improve glucose metabolism. Some studies found that Metformin is capable of reaching lysosomes, increasing their pH; this prevents viral entry into the cells and blocks its replication as viruses need an acidic environment to function. Metformin also protects against secondary fibrosis in the lungs; in the past, it has been successfully used as an anti-influenza drug due to its anti-inflammatory properties. In this review, we will describe these mechanisms more profoundly to better explain the possible effect of anti-diabetic drugs on mortality reduction among COVID-19 patients. With the rapidly growing number of individuals diagnosed with diabetes worldwide, their increased risk of developing severe complications of the COVID-19 infection as well as the emergence of new COVID-19 strains, and the findings suggesting that diabetes is a major risk factor for a severe COVID-19 infection course, we aim to describe the possible anti-viral mechanisms of anti-diabetic drugs, their efficacy in decreasing mortality rates, their possible side effects, and previous studies’ findings. Our study results may offer valuable insights for healthcare professionals when selecting suitable glucose-lowering treatments for diabetics with COVID-19, reducing hospital admissions and the duration of in-hospital stay, as well as helping with better treatment strategies in future viral outbreaks that might progress to pandemics. Additionally, by finding that certain antidiabetic drugs are effective in reducing mortality among diabetics with a COVID-19 infection, we would be able to prioritize these drugs for use in these specific patient populations, potentially helping allocate limited resources more effectively as COVID-19 infections have strained healthcare resources worldwide. Furthermore, antidiabetic drugs are readily available and widely prescribed, so repurposing them for COVID-19 treatment could provide an accessible option for the treatment of diabetics with a COVID-19 infection.