Key words
diabetes - autoimmunity - COVID-19 - SGLT-2 inhibitors - treatment
Importantly, Chen et al. [3] have
demonstrated that COVID-19 may exert a significant deleterious effect on myocardium
and cardiac function. Moreover, some patients with COVID-19 develop acute kidney
injury (AKI), which carries a worse prognosis [4].
Given the importance of DM in the outcomes of COVID-19 [5], antidiabetic treatment options and the
need to achieve adequate glycaemic control are increasingly being discussed [5]
[6]. Of relevance, sodium-glucose
cotransporter 2 inhibitors (SGLT-2is) are known to reduce cardiovascular events and
to protect kidney function [7] in type 2
DM. Thus, it appears worth examining the potential effect of SGLT-2is on preventing
and/or delaying the development of cardiovascular events and AKI in patients
hospitalised with acute COVID-19, regardless of diabetes.
In this setting, two trials with dapagliflozin as a cardioprotective and
renoprotective agent in COVID-19 have already been initiated: DARE-19 (Dapagliflozin
in respiratory failure in patients with COVID-19) [8] and TACTIC-E (Multi-Arm therapeutic
study in pre-ICU patients admitted with Covid-19 - experimental drugs and
mechanisms) [9]. The rationale for these
trials is that SGLT-2is not only improve heart failure and renal function in type 2
DM [7], but they also appear to reduce
inflammation, hypoxia and excess cytokine release [10]
[11]. Importantly, the latter is known to
play a pivotal role in adverse outcomes in COVID-19 [12]
[13]. In DARE-19 (900 participants),
inclusion criteria are hospitalisation for mild-to-moderate COVID-19 (arterial
oxygen saturation ≥ 94% with low-flow supplemental
oxygen) of any duration and at least one of the following: hypertension; type 2 DM;
atherosclerotic cardiovascular disease; heart failure; chronic kidney disease stage
3 to 4 [8]. Patients will be randomised
(1:1) to dapagliflozin 10 mg daily or placebo for 30 days and followed up
for a total of 60 days [8]. The primary
endpoint will be time to first death from any cause or new/aggravated organ
dysfunction [8]. In TACTIC-E, 1407
patients with COVID-19 without need for intensive care unit (ICU) will be enrolled
[9]. These will be randomised (1:1:1)
to either the experimental drug EDP1815 (preparation of a single strain of
Prevotella histicola) or dapagliflozin 10 mg daily plus ambrisentan
(endothelin receptor antagonist) or standard care alone [9]. The primary endpoint will be time to
the composite endpoint comprising death, mechanical ventilation, extracorporeal
membrane oxygenation, cardiovascular support or renal failure [9]. In DARE-19 [8] and TACTIC-E [9], design and endpoints are based on the
known renoprotective and cardioprotective properties of SGLT-2is [7]
[11]
[14] and on accepted meaningful parameters
of COVID-19 clinical course [1]
[2]
[3].
Whether, indeed, SGLT-2is will prove beneficial in this new condition is currently a
matter of investigation and hope. Potential helpful mechanisms include, among
others, increased haematocrit, slight increase of ketone bodies, as well as
reduction of endothelial dysfunction, glomerular hyperfiltration, oxidative stress
and inflammation [9]
[11]
[14]. Certainly, caution is needed until
we obtain tangible data on their utility or otherwise. However, unlike the
Shakespearean hero, we should not lose potential benefits by “fearing to
attempt” [15].
