Anti-inflammatory properties of antidiabetic drugs: A “promised land” in the COVID-19 era?

Abstract

Inflammation is implicated in the development and severity of the coronavirus disease 2019 (COVID-19), as well as in the pathophysiology of diabetes. Diabetes, especially when uncontrolled, is also recognized as an important risk factor for COVID-19 morbidity and mortality. Furthermore, certain inflammatory markers [ i.e. C-reactive protein (CRP), interleukin-6 (IL-6) and ferritin] were reported as strong predictors of worse outcomes in COVID-19 positive patients. The same biomarkers have been associated with poor glycemic control. Therefore, achieving euglycemia in patients with diabetes is even more important in the era of the COVID-19 pandemic. Based on the above, it is clinically interesting to elucidate whether antidiabetic drugs may reduce inflammation, thus possibly minimizing the risk for COVID-19 development and severity. The present narrative review discusses the potential anti-inflammatory properties of certain antidiabetic drugs ( i.e. metformin, pioglitazone, sitagliptin, linagliptin, vildagliptin, alogliptin, saxagliptin, liraglutide, dulaglutide, exenatide, lixisenatide, semaglutide, empagliflozin, dapagliflozin, canagliflozin), with a focus on CRP, IL-6 and ferritin.

Predictors of adverse in-hospital outcome and recovery in patients with diabetes mellitus and COVID-19 pneumonia in Iraq

“…However, five studies with a total of 6937 patients showed that metformin use was associated with reduction in mortality rate from COVID-19 infection [ 17 ]. The potential beneficial effect of metformin noted in COVID-19 infection might be attributed to its inherent anti-inflammatory properties beyond its glucose-lowering action and independent of glucose control, which could positively influence the prognosis and disease course of patients with DM and COVID-19 [ 18 , 19 ].…”

“…[ 5] An upregulation of DPP-4 in patients with DM remains a plausible explanation for the greater severity of COVID-19 in patients with DM [ 20 ]. A recent meta-analysis (n = 1607 patients with DM; 16 trials) found a significant reduction in inflammatory markers following DPP-4 inhibitors use compared with placebo [ 18 , 21 ].…”

<p>COVID-19 and Obesity: Epidemiology, Pathogenesis and Treatment</p>

“…The effect of antidiabetic drugs on the recovery of COVID-19 is beyond the scope of this study, which is reviewed elsewhere. [51][52][53][54]…”

Glucagon‐like peptide‐1 receptor agonists in the era of COVID‐19: Friend or foe?

“…Besides glucose‐lowering effects, a growing body of literature indicates that GLP‐1RAs pose significant anti‐inflammatory properties and pulmonary protective effects. Anti‐inflammatory properties (with a focus on impact on CRP, IL‐6 and ferritin concentrations) of individual GLP‐1RAs have recently been extensively overviewed elsewhere by Katsiki and Ferrannini 30 …”