Intestinal SGLT1 as a therapeutic target in COVID-19-related diabetes: A "two-edged sword" hypothesis

Abstract

Emerging data are linking coronavirus disease 2019 (COVID-19) with an increased risk of developing new-onset diabetes. The gut has been so far out of the frame of the discussion on the pathophysiology of COVID-19-induced diabetes, with the pancreas, liver, and adipose tissue being under the spotlight of medical research. Sodium-glucose co-transporters (SGLT) 1 represent important regulators of glucose absorption, expressed in the small intestine where they mediate almost all sodium-dependent glucose uptake. Similar to what happens in diabetes and other viral infections, SGLT1 upregulation could result in increased intestinal glucose absorption and subsequently promote the development of hyperglycaemia in COVID-19. Considering the above, the question whether dual SGLT (1 and 2) inhibition could contribute to improved outcomes in such cases sounds challenging, deserving further evaluation. Future studies need to clarify whether putative benefits of dual SGLT inhibition in COVID-19 outweigh potential risks, particularly with respect to drug-induced euglycaemic diabetic ketoacidosis, gastrointestinal side effects, and compromised host response to pathogens.

Keywords: COVID-19; SGLT1; SGLT2; diabetes.

FIGURE 1

Potential harms and benefits of dual SGLT (1 and 2) inhibition in COVID‐19‐induced diabetes. Abbreviations: ACE2, angiotensin‐converting enzyme 2; COVID‐19, coronavirus disease 2019; DKA, diabetic ketoacidosis; GI, gastrointestinal; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2; SGLT, sodium‐glucose co‐transporters