A University of Miami researcher has suggested that Tradjenta and other DPP-4 inhibitors may help against COVID-19, the sometimes deadly disease caused by the SARS-CoV-2 coronavirus.
Gianluca Iacobellis, M.D., Ph.D. argued in a commentary that the DPP-4 enzyme is a potential target which should be analyzed further regarding its role in COVID-19.
DPP-4 inhibitors on the market include Tradjenta, Januvia and Janumet. Iacobellis urges that these drugs be tested to see if they can lower inflammation in type 2 diabetes patients with COVID-19. Type 2 diabetes patients are disproportionately experiencing severe COVID-19 symptoms.
A 2013 Nature study found that DPP-4 was a functional receptor for the MERS coronavirus’ spike protein. The MERS coronavirus binds to the DPP-4 receptor and interacts with nuclear factors and T cells which are involved with inflammation. SARS-CoV-2 uses its spike protein to infect host cells, just like the MERS coronavirus.
A 2019 JCI Insight study involved developing a mouse model which could be infected by MERS-CoV by expressing human DPP-4.
DPP-4 inhibition apparently doesn’t reduce infection risk or reduce viral load, but DPP-4 inhibitors have been associated with anti-inflammatory effects. Iacobellis says that might be able to help diabetes patients control immune overreactions caused by COVID-19.
DPP-4 “may represent a potential target for preventing and reducing the risk and the progression of the acute respiratory complications that Type 2 diabetes may add to the COVID-19 infection,” Iacobellis said.
“The body is overreacting with this inflammatory response to the virus,” Iacobellis said. “This could be partially mediated by DPP-4. The virus binds to the enzyme and the enzymatic activity of DPP4 overexpresses inflammatory cytokines, exaggerating the inflammatory response.”
A warning was added to Tradjenta’s label by the U.S. Food and Drug Administration in 2016. It warned of DPP-4 inhibitors being associated with bullous pemphigoid cases requiring hospitalization. Bullous pemphigoid is a rare skin condition which involves large, fluid-filled blisters. It must be treated quickly because it can cause infection and sepsis.
Bullous pemphigoid symptoms include:
• Skin that is itchy prior to blister formation
• Large blisters that do not burst easily when they are touched
• The skin around the blisters can be reddish or darker than usual
• A rash resembling hives
• Blisters or small sores in the mouth or other mucous membranes