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)