Antidiabetes agents
The continuous control and monitoring of blood glucose is of fundamental importance for the diabetes patient, even more so during the COVID-19 pandemic. Patients with diabetes can safely continue to take routine drug therapies, to date there is no evidence that any anti-diabetes therapeutic agent can increase the risk of COVID-19 infection. Even if the patient with diabetes is affected by Sars-Cov-2, one should continue to monitor blood sugar levels and take the usual drug therapy. Probably in case Sars-Cov-2 infection leads the patient into serious complications, possible changes in dosage or medication could be considered, but should always be considered on a case-by-case basis. Several factors, including blood glucose, hemodynamic stability, nutritional status, kidney function, risk of hypoglycemia and drug interactions should be carefully assessed. However, the most commonly used antidiabetes medications in therapy may need to be modified or even discontinued in specific cases. Metformin is among the most commonly used medications for type 2 diabetes and is predominantly eliminated renal, in a COVID-19 patient careful monitoring of renal function should be performed to avoid risk of lactic acidosis caused by increased drug concentrations. Hypoxia may also increase the risk of lactic acidosis. (12) In addition some antivirals used to fight COVID-19 are inhibitors of the organic cation transporter OCT, metformin is a substrate of this transporter, inhibiting OCT may increase metformin concentrations in plasma, careful monitoring should be carried out to avoid this interaction. Some NSAIDs that can be used in the COVID-19 patient may decrease renal function and increase plasma metformin concentration. However, glucocorticoids may increase blood glucose, in which case a change in metformin dose may be considered, although at present the use of glucocorticoids does not seem to be recommended in the COVID-19 patient. Metformin may be discontinued in hospitalised and seriously ill patients due to the risk of lactic acidosis. Agonist glucagon peptide-1 receptor therapy (GLP-1RA) should probably be temporarily discontinued in patients with hemodynamic instability (which impairs absorption from subcutaneous sites), renal dysfunction and gastrointestinal dysfunction. GLP-1RA may cause a slowdown in gastric emptying and may result in clinically significant reductions in the rate and degree of absorption of certain oral drugs administered simultaneously such as darunavir or remdesivir antivirals. (13) Common side effects of GLP-1RA include nausea, vomiting and diarrhoea, which in a COVID-19 patient with similar gastrointestinal symptoms may lead to electrolyte depletion, careful evaluation should be made, GLP-1RA are excreted predominantly renal, in a COVID-19 patient with renal dysfunction an increase in drug concentrations may occur. No particular interactions with anticoagulants such as LHMW or IL1 and 6 inhibitors are known.
Dipeptidil peptidase-4 (DPP4) inhibitors are associated with a low risk of hypoglycemia and are relatively safe in a wide range of renal functions, which is a strength in the COVID-19 patient. Although renal function is severely impaired, a dose modification of drugs in this class should be considered. (14) Another strength of these drugs is that there are no particular interactions with CYP inhibitors, and this is a very important aspect in a COVID-19 patient with diabetes, who is a complex patient and can use highly interacting drugs such as antivirals. Also, there are no particular interactions with anticoagulants. Probably the use of SGLT-2 inhibitors is more complex in the COVID-19 patient, due to the risk of diabetic ketoacidosis, which can lead to potentially fatal cases. (15) The clinical condition of the patient, the concentration of ketone bodies, hyperglycemia, renal function are aspects to be taken into account for a possible suspension of treatment with SGLT-2. In addition, this category of drugs data suggest that the primary route of metabolism in humans is uridine 5′-diphosphorus glucuronidation (UDP) glucuronyltransferase (UGT) 1A3, 1A8, 1A9 and 2B7, and they are also OCT substrates. Interaction with antivirals such as darunavir and remdesivir should be carefully considered. There are no particular interactions with LHMW or IL-1 and 6 inhibitors. Insulin use should be carefully monitored due to the risk of hypoglycemia, and a dose change should be considered if the patient is on glucocorticoid therapy. In addition, a possible hypoglycemic additive effect due to hydroxychloroquine should be carefully evaluated. In patients with COVID-19 on sulfoniluree therapy, a change to insulin therapy should be considered because of the risk of high hypoglycemia in patients with Sars-Cov-2 infection. Caution with sulfonylureas should also be exercised in consideration of chloroquine, due to the risk of hypoglycaemia with both and if renal dysfunction is present. (16)
Thiazolidinediones such as pioglitazone should be carefully questioned for use in the COVID-19 patient, as this class of drugs is contraindicated in patients with hemodynamic instability, liver or cardiac dysfunction, which may be present in a severe COVID-19 infection Currently, existing evidence suggests that insulin is used compared to agents such as sulfonylureas or thiazolidinediones. (Figure 1)