Clinical Trial of Pioglitazone Treatment in Patients With Type 2 Diabetes Mellitus and Covid-19

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.