Approximately 10-15% of patients infected with COVID-19 develop severe illness characterized by respiratory distress, increased risk of clotting disease, myocardial damage, stroke and mortality. Subjects with Type 2 diabetes (T2DM) are at increased risk for severe COVID-19 disease. Exuberant inflammatory and immune responses were suggested as the etiology responsible for the development of severe COVID-19 disease. The increased chronic inflammatory state characteristic of T2DM could contribute to the increased risk of severe COVID-19 disease in T2DM patients. Therefore, its possible that anti-inflammatory therapy will reduce the risk of severe COVID-19 disease. Consistent with this assumption, a recent study has reported that steroid therapy improves the outcome in patients with severe COVID-19 disease.

The medication pioglitazone is a strong insulin sensitizer that reduces plasma glucose concentrations in T2DM patients. In addition to improving insulin sensitivity, several studies have demonstrated that pioglitazone reduces chronic inflammation in T2DM patients, which is manifested in a decrease in TNF-alpha, interleukin, hs CRP, leptin and other inflammatory markers in T2DM treated with pioglitazone. Further, pioglitazone enhances the plasma level of anti-inflammatory agents. For example, the plasma level of 15-epi-lipoxin A, a lipid mediator with strong anti-inflammatory and inflammation-resolving effects that has been reported to neutralize RNA coated viruses, is significantly elevated by pioglitazone treatment in T2DM patients. Therefore, we hypothesize that administering pioglitazone to T2DM patients who have moderate-to-severe COVID-19 will improve the clinical outcome of their COVID-19 disease.