Evaluating the effects of sodium glucose co-transporter -2 inhibitors from a renin–angiotensin–aldosterone system perspective in patients infected with COVID-19: contextualizing findings from the dapagliflozin in respiratory failure in patients with COVID-19 study

Abstract

Numerous studies demonstrate parallels between CVD, type 2 diabetes mellitus (T2DM) and COVID-19 pathology, which accentuate pre-existing complications in patients infected with COVID-19 and potentially exacerbate the infection course. Antidiabetic drugs such as sodium-glucose transporter-2 (SGLT-2) inhibitors have garnered substantial attention recently due to their efficacy in reducing the severity of cardiorenal disease. The effect of SGLT-2 inhibitors in patients with COVID-19 remains unclear particularly since SGLT-2 inhibitors contribute to altering the RAAS cascade activity, which includes ACE-2, the major cell entry receptor for SARS-CoV2. A study, DARE-19, was carried out to unveil the effects of SGLT-2 inhibitor treatment on comorbid disease complications and concomitant COVID-19 outcomes and demonstrated no statistical significance. However, the need for further studies is essential to provide conclusive clinical findings.

Susceptibility to recombinant SARS‐CoV‐2 spike protein entry in the lungs of high‐fat diet‐induced obese mice

“…50 Recent studies suggest possible beneficial effects of noninsulin antihyperglycemic agents against SARS-CoV-2 infection, such as dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and glucagon-like peptide-1 (GLP-1) receptor agonists. [51][52][53][54][55] The current study has several limitations: (i) more examinations with human ACE2-transgenic mice might be considered to confirm the conclusion of this study. (ii) This experimental model is limited with respect to pathophysiology.…”

“…Other research has shown that there is no association between mineralocorticoid receptor antagonist usage and mortality in COVID‐19 50 . Recent studies suggest possible beneficial effects of noninsulin antihyperglycemic agents against SARS‐CoV‐2 infection, such as dipeptidyl peptidase‐4 inhibitors (DPP4i), sodium‐glucose cotransporter‐2 inhibitors (SGLT2i), and glucagon‐like peptide‐1 (GLP‐1) receptor agonists 51–55 …”

Insulin may increase disease severity and mortality of COVID-19 through Na+/H+ exchanger in patients with type 1 and type 2 diabetes mellitus

“…Metformin and DPP-4 inhibitors have been shown to have beneficial effects in the COVID-19 treatment [ 26 – 28 ]. Although the use of SGLT2 inhibitors in COVID-19 is still controversial, there is no clear evidence that they increase mortality and progression in COVID-19 [ 29 ]. However, there is also no evidence proving that SGLT2 inhibitors have a beneficial effect on COVID-19 [ 2 ].…”