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Sir,
The observations provided in the letter “Sodium–glucose cotransporter 2 inhibitors [SGLT2-i] and major COVID-19 outcomes: promising mechanisms, conflicting data, and intriguing clinical decisions” [1] are completely agreeable. The authors recall the potential pleiotropic effects of these drugs, providing potential benefits that go beyond the improvement of glucose control in patients with type 2 diabetes (and in subjects with type 1 diabetes), underlying the cardiovascular and renal advantages even in subjects without diabetes. Other potential therapeutic activities of SGLT2-i have been tested in hypertension (thanks to their peculiar natriuretic activity, different from that obtained by classical diuretics) [2]; obesity and NAFLD (non-alcoholic fatty liver disease), considering their induced weight loss and their activity on visceral adipose tissue which lead to a reduction in hepatic steatosis [3, 4]; gout (thanks to the increased urate excretion) [5]; SIADH (syndrome of inappropriate ADH secretion), by means of their potential effect on free-water clearance in addition to fluid restriction [6]; and PCOS (polycystic ovarian syndrome) owing to their action on hyperglycemia and overweight [7].
It should be of interest to emphasize some more activities exerted by the drugs of this class on respiratory function. For instance, patients suffering from obstructive sleep apnea syndrome (OSAS) may benefit from the weight loss obtained with SGLT2-i [8]. Furthermore, empagliflozin was able to lower mortality in experimental pulmonary hypertension. This result was partially explained by the observed reduced pulmonary remodelling [9]. Interestingly, SGLT2 was recognized as a potential marker of indeterminate lung nodules: its activity may help in identifying metabolically active lung premalignancy and early-stage lung adenocarcinoma [10]. As a matter of fact, SGLT2 is expressed early in lung carcinogenesis: its activity could be observed in patients by means of positron emission tomography (PET) with a specific tracer (Me4FDG: methyl-4[18F]-4-deoxyglucose). SGLT2-i suppress growth of early stage lung adenocarcinoma and may afford an extended survival in animal models. These observations shed some more light on the so-called pleiotropic activity of this class of drugs, although more data are warranted to better understand their therapeutic possibilities both in pulmonary diseases and in respiratory failure in patients with COVID-19. Concerning this latter point, the outcomes of the Dapagliflozin in Respiratory Failure in Patients with COVID-19 (DARE-19) trial (ClinicalTrials.gov identifier NCT04350593) should provide more evidence.
References
Patoulias D, Papadopoulos C, Katsimardou A, Toumpourleka M, Doumas M. Sodium–glucose cotransporter 2 inhibitors and major COVID-19 outcomes: promising mechanisms, conflicting data, and intriguing clinical decisions. Adv Ther. 2020. https://doi.org/10.1007/s13300-020-00942-7.
Verma S. Potential mechanisms of sodium-glucose co-transporter 2 inhibitor-related cardiovascular benefits. Am J Cardiol. 2019;15(124):S36–44.
Scheen AJ. Beneficial effects of SGLT2 inhibitors on fatty liver in type 2 diabetes: a common comorbidity associated with severe complications. Diabetes Metab. 2019;45(3):213–23.
Kuchay MS, Krishan S, Mishra SK, et al. Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: a randomized controlled trial (E-LIFT trial). Diabetes Care. 2018;41(8):1801–8.
Bailey CJ. Uric acid and the cardio-renal effects of SGLT2 inhibitors. Diabetes Obes Metab. 2019;21(6):1291–8. https://doi.org/10.1111/dom.13670.
Refardt J, Winzeler B, Meienberg F, Vogt DR, Christ-Crain M. Empagliflozin increases short-term urinary volume output in artificially induced syndrome of inappropriate antidiuresis. Int J Endocrinol. 2017. https://doi.org/10.1155/2017/7815690.
Javed Z, Papageorgiou M, Deshmukh H, et al. Effects of empagliflozin on metabolic parameters in polycystic ovary syndrome: a randomized controlled study. Clin Endocrinol. 2019;90(6):805–13.
Sawada K, Karashima S, Kometani M, et al. Effect of sodium glucose cotransporter 2 inhibitors on obstructive sleep apnea in patients with type 2 diabetes. Endocr J. 2018;65(4):461–7.
Chowdhury B, Luu VZ, Luu AZ, et al. The SGLT2 inhibitor empagliflozin reduces mortality in experimental pulmonary hypertension. Eur Heart J. 2019;40(Suppl 1):ehz747.0009. https://doi.org/10.1093/eurheartj/ehz747.0009.
Scafoglio CR, Villegas B, Abdelhady G, et al. Sodium-glucose transporter 2 is a diagnostic and therapeutic target for early stage lung adenocarcinoma. Sci Transl Med. 2018;10:467. https://doi.org/10.1126/scitranslmed.aat5933.
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Antonio C. Bossi, Franco Forloni and Paolo L. Colombelli have nothing to disclose.
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This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
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Bossi, A.C., Forloni, F. & Colombelli, P.L. A Response To: Sodium–Glucose Cotransporter 2 Inhibitors and Major COVID-19 Outcomes: Promising Mechanisms, Conflicting Data, and Intriguing Clinical Decisions. Diabetes Ther 11, 3007–3009 (2020). https://doi.org/10.1007/s13300-020-00943-6
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DOI: https://doi.org/10.1007/s13300-020-00943-6