Glucometabolic perturbations in type 2 diabetes mellitus and coronavirus disease 2019: causes, consequences, and how to counter them using novel antidiabetic drugs

The growing amount of evidence suggests the existence of a bidirectional relation between coronavirus disease 2019 (COVID-19) and type 2 diabetes mellitus (T2DM), as these two conditions are worsening each other, causing a significant healthcare and socioeconomic burden. The alterations in innate and adaptive cellular immunity, adipose tissue, alveolar, and endothelial dysfunction, hypercoagulation, propensity to an increased viral load, and chronic diabetic complications are all associated with glucometabolic perturbations characteristic for T2DM patients, and predispose them to severe forms and mortality of COVID-19. On the other hand, severe acute respiratory syndrome coronavirus 2 infection negatively impacts glucose homeostasis due to its effects on insulin sensitivity and β-cell function, further aggravating the preexisting glucometabolic perturbations in individuals with T2DM. Thus, we are in the urgent need for the most effective ways of countering these glucometabolic disturbances occurring during the acute COVID-19 illness in T2DM patients. The novel classes of antidiabetic medications (dipeptidyl peptidase 4 inhibitors (DPP-4is), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are considered as candidate drugs for this purpose. The aim of this review article was to summarize current knowledge regarding the glucometabolic disturbances during acute COVID-19 illness in T2DM patients and the potential ways to tackle those using novel antidiabetic medications. Recent observational data suggest that preadmission use of GLP-1 RAs and SGLT-2is are associated with a decreased, while the preadmission use of DPP-4is is associated with an increased in-hospital mortality of T2DM patients with COVID-19. Although these results provide further evidence for the widespread use of these two classes of medications in the COVID-19 era, dedicated randomized controlled trials analyzing the effects of in-hospital use of novel antidiabetic agents in T2DM patients with COVID-19 are needed.