• Daniel Gonikman and Dmitrijs Kustovs.
• Student of Faculty of Medicine, Riga Stradins University, LV-1007 Riga, Latvia.
• Medicina (Kaunas). 2023 Oct 11; 59 (10).

AbstractBackground and Objectives: The COVID-19 pandemic caused by the Coronavirus SARS-CoV-2 is a complex challenge for the existing scientific and medical landscape. It is an ongoing public health crisis, with over 245,373,039 confirmed cases globally, including 4,979,421 deaths as of 29 October 2021. Exploring molecular mechanisms correlated with the disease's severity has demonstrated significant factors of immune compromise, noted in diabetic patients with SARS-CoV-2 infections. Among diabetics, the altered function of the immune system allows for better penetration of the virus into epithelial cells, increased viral binding affinity due to hyperglycemia, reduced T cell function, decreased viral clearance, high risks of cytokine storm, and hyper-inflammatory responses, altogether increasing the susceptibility of these patients to an extreme COVID-19 disease course. Materials and Methods: This research involved a systematic literature search among various databases comprising PubMed and Google Scholar in determining credible studies about the effects of antidiabetic drugs on the high mortality rates among diabetic patients infected with COVID-19. The primary search found 103 results. Duplicated results, non-pertinent articles, and the unavailability of full text were excluded. Finally, we included 74 articles in our review. The inclusion criteria included articles published during 2020-2023, studies that reported a low risk of bias, and articles published in English. Exclusion criteria included studies published in non-peer-reviewed sources, such as conference abstracts, thesis papers, or non-academic publications. Results: Among the studied anti-diabetic drugs, Metformin, the Glucagon-like peptide 1 receptor agonist (GLP-1RA), and Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) have demonstrated decreased mortality rates among diabetic patients infected with COVID-19. Insulin and Dipeptidyl peptidase 4 inhibitors (DPP-4i) have demonstrated increased mortality rates, while Sulfonylureas, Thiazolidinedione (TZD), and Alpha-glucosidase inhibitors (AGI) have demonstrated mortality-neutral results.

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