The treatment with pioglitazone added to the standard treatment of patients with DM2 hospitalized for COVID-19 may produce a decrease in the number of patients who progress to a second phase of severe systemic inflammation.
According to the latest studies, the evolution of the SARS-CoV-2 (COVID-19) infection shows
two clinically different phases: The first phase of viral and clinical infection of viriasis
(fever, myalgia, etc.) affects all patients and it is resolved in asymptomatic patients or
with clinically moderate-mild affectations. However, towards the end of the first week of
illness, a not inconsiderable number of patients progress towards a second phase of rapid and
abrupt deterioration of their respiratory and cardiac function.
More and more data indicate an important role of overactivated macrophages, interleukin 6
(IL6) and an excessive inflammatory response in the genesis of this second phase of
aggravation. Linking with this hypothesis, the adipose tissue densely infiltrated by
macrophages is the source of one third of the body's IL6, its production being even greater
in the fat of central disposition of male distribution. All of this could explain the worse
prognosis observed in men, obese and with type 2 diabetes (DM2).
Regarding the possible effect of pioglitazone on the expression of ACE2, there is little
literature, and less evidence, about the response of this receptor to treatment with
pioglitazone, and what is more important, its effect on COVID-19 infection.
Two studies have analyzed the expression of this receptor after administration of
pioglitazone in different murine models of liver and kidney disease. The conclusions of these
studies were that the administration of pioglitazone in rats with hepatic steatosis increased
the expression of ACE2. It is known that the increased expression of ACE2 facilitates the
entry of SARS-CoV-2 into the cell, in animal models it has been seen that ACE2 protects
against the development of respiratory distress syndrome and that severe cases of COVID-19
and SARS 2003 have been linked to the possible inhibition of ACE2 by the virus and the
increase in angiotensin II.
In conclusion, it is a safe and proven drug in patients with DM2, cheap, with years of
clinical experience. The use of pioglitazone added to the conventional treatment of patients
at high risk, such as patients with COVID-19 and DM2, could be accompanied by a better
evolution of the patients, avoiding or mitigating the inflammatory process that already
occurs before its onset. seems to trigger the second accelerated phase of the disease.
Drug: Pioglitazone 30 mg
Patients receive 30 mg/day of pioglitazone for the entire period they remain in hospital
Other: standard of care
Patients receive the standard of care, according to the hospital protocol for patients with type 2 diabetes mellitus hospitalized.
Inclusion Criteria:
1. Adult patients > 18 years
2. Confirmed diagnosis of COVID-19 or high clinical suspicion according to current
criteria.
3. Diagnosis prior to admission of DM2.
4. Patients who provide their informed consent to participate in the study
Exclusion Criteria:
1. Under 18 years
2. Known hypersensitivity to the active ingredient or any of the drug's excipients.
3. Known history of heart failure or situation at the time of initiation of the heart
failure study.
4. Hepatic failure.
5. Dialysis
6. Situation of diabetic ketoacidosis at the start of the study.
7. Diabetes mellitus different from type 2.
8. Active bladder cancer or a history of bladder cancer
9. Hematuria
10. Patients included in another experimental study with another drug.
11. Admission to the Intensive Care Unit.
12. Patients requiring mechanical ventilation at the time of inclusion
13. Pregnancy
14. Lactation
Hospital Ramón y Cajal
Madrid, Spain