Why have SGLT2 Inhibitors Failed to Achieve the Desired Success in COVID-19?


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Abstract

:The SARS-CoV-2 virus emerged towards the end of 2019 and caused a major worldwide pandemic lasting at least 2 years, causing a disease called COVID-19. SARS-CoV-2 caused a severe infection with direct cellular toxicity, stimulation of cytokine release, increased oxidative stress, disruption of endothelial structure, and thromboinflammation, as well as angiotensin-converting enzyme 2 (ACE2) down-regulation-mediated renin-angiotensin system (RAS) activation. In addition to glucosuria and natriuresis, sodium-glucose transport protein 2 (SGLT2) inhibitors (SGLT2i) cause weight loss, a decrease in glucose levels with an insulin-independent mechanism, an increase in erythropoietin levels and erythropoiesis, an increase in autophagy and lysosomal degradation, Na+/H+-changer inhibition, prevention of ischemia/reperfusion injury, oxidative stress and they have many positive effects such as reducing inflammation and improving vascular function. There was great anticipation for SGLT2i in treating patients with diabetes with COVID-19, but current data suggest they are not very effective. Moreover, there has been great confusion in the literature about the effects of SGLT2i on COVID-19 patients with diabetes . Various factors, including increased SGLT1 activity, lack of angiotensin receptor blocker co-administration, the potential for ketoacidosis, kidney injury, and disruptions in fluid and electrolyte levels, may have hindered SGLT2i's effectiveness against COVID-19. In addition, the duration of use of SGLT2i and their impact on erythropoiesis, blood viscosity, cholesterol levels, and vitamin D levels may also have played a role in their failure to treat the virus. This article aims to uncover the reasons for the confusion in the literature and to unravel why SGLT2i failed to succeed in COVID-19 based on some solid evidence as well as speculative and personal perspectives.

About the authors

Medine Cumhur Cure

Department of Biochemistry, Medilab Laboratory and Imaging Center

Email: info@benthamscience.net

Erkan Cure

Department of Internal Medicine, Beylikdüzü Medilife Hospital

Author for correspondence.
Email: info@benthamscience.net

References

  1. Ionescu M, Stoian AP, Rizzo M, et al. The role of endothelium in COVID-19. Int J Mol Sci 2021; 22(21): 11920. doi: 10.3390/ijms222111920 PMID: 34769350
  2. Ramos SG, Rattis BAC, Ottaviani G, Celes MRN, Dias EP. ACE2 down-regulation may act as a transient molecular disease causing RAAS dysregulation and tissue damage in the microcirculatory environment among COVID-19 patients. Am J Pathol 2021; 191(7): 1154-64. doi: 10.1016/j.ajpath.2021.04.010 PMID: 33964216
  3. Higashikuni Y, Liu W, Obana T, Sata M. Pathogenic basis of thromboinflammation and endothelial injury in COVID-19: Current findings and therapeutic implications. Int J Mol Sci 2021; 22(21): 12081. doi: 10.3390/ijms222112081 PMID: 34769508
  4. Bell RM, Yellon DM. SGLT2 inhibitors: Hypotheses on the mechanism of cardiovascular protection. Lancet Diabetes Endocrinol 2018; 6(6): 435-7. doi: 10.1016/S2213-8587(17)30314-5 PMID: 29030201
  5. Vallon V, Verma S. Effects of SGLT2 inhibitors on kidney and cardiovascular function. Annu Rev Physiol 2021; 83(1): 503-28. doi: 10.1146/annurev-physiol-031620-095920 PMID: 33197224
  6. Verma S. Potential mechanisms of sodium-glucose co-transporter 2 inhibitor-related cardiovascular benefits. Am J Cardiol 2019; 124 (Suppl. 1): S36-44. doi: 10.1016/j.amjcard.2019.10.028 PMID: 31741439
  7. Gonikman D, Kustovs D. Antidiabetic drug efficacy in reduction of mortality during the COVID-19 pandemic. Medicina 2023; 59(10): 1810. doi: 10.3390/medicina59101810 PMID: 37893528
  8. Zhan K, Weng L, Qi L, et al. Effect of antidiabetic therapy on clinical outcomes of COVID-19 patients with type 2 diabetes: A systematic review and meta-analysis. Ann Pharmacother 2023; 57(7): 776-86. doi: 10.1177/10600280221133577 PMID: 36314281
  9. Ferrannini G, Lund LH, Benson L, et al. Association between use of novel glucose-lowering drugs and COVID-19 hospitalization and death in patients with type 2 diabetes: A nationwide registry analysis. Eur Heart J Cardiovasc Pharmacother 2022; 9(1): 10-7. doi: 10.1093/ehjcvp/pvac044 PMID: 35963647
  10. Abani O, Abbas A, Abbas F, et al. Empagliflozin in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. Lancet Diabetes Endocrinol 2023; 11(12): 905-14. doi: 10.1016/S2213-8587(23)00253-X PMID: 37865101
  11. Zimmermann P, Sourij H, Aberer F, Rilstone S, Schierbauer J, Moser O. SGLT2 inhibitors in long COVID syndrome: Is there a potential role? J Cardiovasc Dev Dis 2023; 10(12): 478. doi: 10.3390/jcdd10120478 PMID: 38132646
  12. Jackson CB, Farzan M, Chen B, Choe H. Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol 2022; 23(1): 3-20. doi: 10.1038/s41580-021-00418-x PMID: 34611326
  13. Fountain JH, Kaur J, Lappin SL. Physiology, renin angiotensin system. StatPearls. Treasure Island, FL: StatPearls Publishing 2023.
  14. Garcia B, Zarbock A, Bellomo R, Legrand M. The alternative renin–angiotensin system in critically ill patients: pathophysiology and therapeutic implications. Crit Care 2023; 27(1): 453. doi: 10.1186/s13054-023-04739-5 PMID: 37986086
  15. Sequeira-Lopez MLS, Gomez RA. Renin cells, the kidney, and hypertension. Circ Res 2021; 128(7): 887-907. doi: 10.1161/CIRCRESAHA.121.318064 PMID: 33793334
  16. AlQudah M, Hale TM, Czubryt MP. Targeting the renin-angiotensin-aldosterone system in fibrosis. Matrix Biol 2020; 91-92: 92-108. doi: 10.1016/j.matbio.2020.04.005 PMID: 32422329
  17. Dasgupta C, Zhang L. Angiotensin II receptors and drug discovery in cardiovascular disease. Drug Discov Today 2011; 16(1-2): 22-34. doi: 10.1016/j.drudis.2010.11.016 PMID: 21147255
  18. Siragy HM, Angiotensin II. Angiotensin II subtype 2 receptor: Potential therapy. J Clin Hypertens 2009; 11(s12) (Suppl. 12): S26-9. doi: 10.1111/j.1751-7176.2009.00212.x
  19. Sansoè G, Aragno M. New viral diseases and new possible remedies by means of the pharmacology of the renin-angiotensin system. J Renin Angiotensin Aldosterone Syst 2023; 2023: 3362391. doi: 10.1155/2023/3362391 PMID: 37476705
  20. Muhanna D, Arnipalli SR, Kumar SB, Ziouzenkova O. Osmotic adaptation by Na+-dependent transporters and ACE2: Correlation with hemostatic crisis in COVID-19. Biomedicines 2020; 8(11): 460. doi: 10.3390/biomedicines8110460 PMID: 33142989
  21. Monteil V, Kwon H, Prado P, et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell 2020; 181(4): 905-913.e7. doi: 10.1016/j.cell.2020.04.004 PMID: 32333836
  22. Dutka M, Bobiński R, Ulman-Włodarz I, et al. Sodium glucose cotransporter 2 inhibitors: Mechanisms of action in heart failure. Heart Fail Rev 2021; 26(3): 603-22. doi: 10.1007/s10741-020-10041-1 PMID: 33150520
  23. Ansary TM, Nakano D, Nishiyama A. Diuretic effects of sodium glucose cotransporter 2 inhibitors and their influence on the renin-angiotensin system. Int J Mol Sci 2019; 20(3): 629. doi: 10.3390/ijms20030629 PMID: 30717173
  24. Puglisi S, Rossini A, Poli R, et al. Effects of SGLT2 inhibitors and GLP-1 receptor agonists on renin-angiotensin-aldosterone system. Front Endocrinol 2021; 12: 738848. doi: 10.3389/fendo.2021.738848 PMID: 34745006
  25. Lopaschuk GD, Verma S. Mechanisms of cardiovascular benefits of sodium glucose co-transporter 2 (SGLT2) inhibitors. JACC Basic Transl Sci 2020; 5(6): 632-44. doi: 10.1016/j.jacbts.2020.02.004 PMID: 32613148
  26. Mudaliar S, Polidori D, Zambrowicz B, Henry RR. Sodium–glucose cotransporter inhibitors: Effects on renal and intestinal glucose transport. Diabetes Care 2015; 38(12): 2344-53. doi: 10.2337/dc15-0642 PMID: 26604280
  27. Zelniker TA, Braunwald E. Mechanisms of cardiorenal effects of sodium-glucose cotransporter 2 inhibitors. J Am Coll Cardiol 2020; 75(4): 422-34. doi: 10.1016/j.jacc.2019.11.031 PMID: 32000955
  28. Martins CNG, Bau AA, Silva LM, Coelho OR. Possible mechanisms of action of SGLT2 inhibitors in heart failure. ABC: Heart Fail Cardiomyopathy 2021; 1(1): 33-43. doi: 10.36660/abchf.20210007
  29. Vaziri Z, Saleki K, Aram C, et al. Empagliflozin treatment of cardiotoxicity: A comprehensive review of clinical, immunobiological, neuroimmune, and therapeutic implications. Biomed Pharmacother 2023; 168: 115686. doi: 10.1016/j.biopha.2023.115686 PMID: 37839109
  30. Sawamura T, Karashima S, Nagase S, et al. Effect of sodium–glucose cotransporter-2 inhibitors on aldosterone-to-renin ratio in diabetic patients with hypertension: A retrospective observational study. BMC Endocr Disord 2020; 20(1): 177. doi: 10.1186/s12902-020-00656-8 PMID: 33256676
  31. Sarzani R, Giulietti F, Di Pentima C, Spannella F. Sodium-glucose co-transporter-2 inhibitors: peculiar "hybrid" diuretics that protect from target organ damage and cardiovascular events. Nutr Metab Cardiovasc Dis 2020; 30(10): 1622-32. doi: 10.1016/j.numecd.2020.05.030 PMID: 32631704
  32. Kravtsova O, Bohovyk R, Levchenko V, et al. SGLT2 inhibition effect on salt-induced hypertension, RAAS, and Na+ transport in Dahl SS rats. Am J Physiol Renal Physiol 2022; 322(6): F692-707. doi: 10.1152/ajprenal.00053.2022 PMID: 35466690
  33. Cherney DZI, Perkins BA, Soleymanlou N, et al. Sodium glucose cotransport-2 inhibition and intrarenal RAS activity in people with type 1 diabetes. Kidney Int 2014; 86(5): 1057-8. doi: 10.1038/ki.2014.246 PMID: 25360497
  34. Nassar M, Abosheaishaa H, Singh AK, Misra A, Bloomgarden Z. Noninsulin-based antihyperglycemic medications in patients with diabetes and COVID-19: A systematic review and meta-analysis. J Diabetes 2023; 15(2): 86-96. doi: 10.1111/1753-0407.13359 PMID: 36690377
  35. Li XT, Zhang MW, Zhang ZZ, et al. Abnormal apelin-ACE2 and SGLT2 signaling contribute to adverse cardiorenal injury in patients with COVID-19. Int J Cardiol 2021; 336: 123-9. doi: 10.1016/j.ijcard.2021.05.029 PMID: 34000358
  36. Li HL, Tse YK, Chandramouli C. Sodium-glucose cotransporter 2 inhibitors and the risk of pneumonia and septic shock. J Clin Endocrinol Metab 2022; 107(12): 3442-51. doi: 10.1210/clinem/dgac558
  37. Kosiborod M, Berwanger O, Koch GG, et al. Effects of dapagliflozin on prevention of major clinical events and recovery in patients with respiratory failure because of COVID-19: Design and rationale for the DARE-19 study. Diabetes Obes Metab 2021; 23(4): 886-96. doi: 10.1111/dom.14296 PMID: 33319454
  38. Koufakis T, Maltese G, Metallidis S, Zebekakis P, Kotsa K. Looking deeper into the findings of DARE-19: Failure or an open door to future success? Pharmacol Res 2021; 173: 105872. doi: 10.1016/j.phrs.2021.105872 PMID: 34487851
  39. Jimbo M, Saito S, Uematsu T, et al. Risk analysis of COVID-19 hospitalization and critical care by race and region in the United States: A cohort study. BMC Public Health 2023; 23(1): 1489. doi: 10.1186/s12889-023-16401-4 PMID: 37542210
  40. Foresta A, Ojeda-Fernandez L, Macaluso G, et al. Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors and COVID-19 outcomes. Clin Ther 2023; 45(4): e115-26. doi: 10.1016/j.clinthera.2023.02.007 PMID: 36933975
  41. Nguyen NN, Ho DS, Nguyen HS, et al. Preadmission use of antidiabetic medications and mortality among patients with COVID-19 having type 2 diabetes: A meta-analysis. Metabolism 2022; 131: 155196. doi: 10.1016/j.metabol.2022.155196 PMID: 35367460
  42. Gupta K, Kunal S. SGLT-2 inhibitors as cardioprotective agents in COVID-19. Heart Lung 2020; 49(6): 875-6. doi: 10.1016/j.hrtlng.2020.09.002 PMID: 33010945
  43. Salgado-Barreira A, Seijas-Amigo J, Rodriguez-Mañero M, et al. Effect of dapagliflozin on COVID-19 infection and risk of hospitalization. J Antimicrob Chemother 2023; 78(9): 2335-42. doi: 10.1093/jac/dkad241 PMID: 37549309
  44. Tisch C, Xourgia E, Exadaktylos A, Ziaka M. Potential use of sodium glucose co-transporter 2 inhibitors during acute illness: A systematic review based on COVID-19. Endocrine 2024. doi: 10.1007/s12020-024-03758-8 PMID: 38448675
  45. Koufakis T, Metallidis S, Zebekakis P, Kotsa K. Intestinal SGLT1 as a therapeutic target in COVID-19-related diabetes: A "two-edged sword" hypothesis. Br J Clin Pharmacol 2021; 87(10): 3643-6. doi: 10.1111/bcp.14800 PMID: 33684969
  46. Zhao M, Li N, Zhou H. SGLT1: A potential drug target for cardiovascular disease. Drug Des Devel Ther 2023; 17: 2011-23. doi: 10.2147/DDDT.S418321 PMID: 37435096
  47. Park SH, Belcastro E, Hasan H, et al. Angiotensin II-induced upregulation of SGLT1 and 2 contributes to human microparticle-stimulated endothelial senescence and dysfunction: Protective effect of gliflozins. Cardiovasc Diabetol 2021; 20(1): 65. doi: 10.1186/s12933-021-01252-3 PMID: 33726768
  48. Xie L, Zhang Z, Wang Q, Chen Y, Lu D, Wu W. COVID-19 and diabetes: A comprehensive review of angiotensin converting enzyme 2, mutual effects and pharmacotherapy. Front Endocrinol 2021; 12: 772865. doi: 10.3389/fendo.2021.772865 PMID: 34867819
  49. Sumners C, de Kloet AD, Krause EG, Unger T, Steckelings UM. Angiotensin type 2 receptors: Blood pressure regulation and end organ damage. Curr Opin Pharmacol 2015; 21: 115-21. doi: 10.1016/j.coph.2015.01.004 PMID: 25677800
  50. Hernandez AF, Green JB, Janmohamed S, et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): A double-blind, randomised placebo-controlled trial. Lancet 2018; 392(10157): 1519-29. doi: 10.1016/S0140-6736(18)32261-X PMID: 30291013
  51. Beyerstedt S, Casaro EB, Rangel ÉB. COVID-19: Angiotensin- converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection. Eur J Clin Microbiol Infect Dis 2021; 40(5): 905-19. doi: 10.1007/s10096-020-04138-6 PMID: 33389262
  52. Zhang T, Wang X, Wang Z, et al. Canagliflozin ameliorates ventricular remodeling through apelin/angiotensin-converting enzyme 2 signaling in heart failure with preserved ejection fraction rats. Pharmacology 2023; 108(5): 478-91. doi: 10.1159/000533277 PMID: 37611563
  53. Blau JE, Tella SH, Taylor SI, Rother KI. Ketoacidosis associated with SGLT2 inhibitor treatment: Analysis of FAERS data. Diabetes Metab Res Rev 2017; 33(8): e2924. doi: 10.1002/dmrr.2924
  54. Khedr A, Hennawi HA, Khan MK, et al. Sodium-glucose cotransporter-2 inhibitor-associated euglycemic diabetic ketoacidosis in COVID-19-infected patients: A systematic review of case reports. World J Clin Cases 2023; 11(24): 5700-9. doi: 10.12998/wjcc.v11.i24.5700 PMID: 37727728
  55. Khunti K, Del Prato S, Mathieu C, Kahn SE, Gabbay RA, Buse JB. COVID-19, hyperglycemia, and new-onset diabetes. Diabetes Care 2021; 44(12): 2645-55. doi: 10.2337/dc21-1318 PMID: 34625431
  56. Tsimihodimos V, Filippas-Ntekouan S, Elisaf M. SGLT1 inhibition: Pros and cons. Eur J Pharmacol 2018; 838: 153-6. doi: 10.1016/j.ejphar.2018.09.019 PMID: 30240793
  57. Zou H, Zhou B, Xu G. SGLT2 inhibitors: A novel choice for the combination therapy in diabetic kidney disease. Cardiovasc Diabetol 2017; 16(1): 65. doi: 10.1186/s12933-017-0547-1 PMID: 28511711
  58. Barreto EA, Cruz AS, Veras FP, et al. COVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesis. Proc Natl Acad Sci USA 2023; 120(21): e2217119120. doi: 10.1073/pnas.2217119120 PMID: 37186819
  59. Khunti K, Ruan Y, Davies J, et al. Association between SGLT2 inhibitor treatment and diabetic ketoacidosis and mortality in people with type 2 diabetes admitted to hospital with COVID-19. Diabetes Care 2022; 45(12): 2838-43. doi: 10.2337/dc22-0357 PMID: 36074663
  60. Selby NM, Forni LG, Laing CM, et al. COVID-19 and acute kidney injury in hospital: Summary of NICE guidelines. BMJ 2020; 369: m1963. doi: 10.1136/bmj.m1963 PMID: 32457068
  61. Pourfridoni M, Abbasnia SM, Shafaei F, Razaviyan J, Heidari- Soureshjani R. Fluid and electrolyte disturbances in COVID-19 and their complications. BioMed Res Int 2021; 2021: 1-5. doi: 10.1155/2021/6667047 PMID: 33937408
  62. Heerspink HJL, Furtado RHM, Berwanger O, et al. Dapagliflozin and kidney outcomes in hospitalized patients with COVID-19 infection. Clin J Am Soc Nephrol 2022; 17(5): 643-54. doi: 10.2215/CJN.14231021 PMID: 35483733
  63. Vargas-Delgado AP, Arteaga Herrera E, Tumbaco Mite C, Delgado Cedeno P, Van Loon MC, Badimon JJ. Renal and cardiovascular metabolic impact caused by ketogenesis of the SGLT2 inhibitors. Int J Mol Sci 2023; 24(4): 4144. doi: 10.3390/ijms24044144 PMID: 36835554
  64. Muskiet MHA, van Raalte DH, van Bommel EJM, Smits MM, Tonneijck L. Understanding EMPA-REG OUTCOME. Lancet Diabetes Endocrinol 2015; 3(12): 928-9. doi: 10.1016/S2213-8587(15)00424-6 PMID: 26590679
  65. Permana H, Audi Yanto T, Ivan Hariyanto T. Pre-admission use of sodium glucose transporter-2 inhibitor (SGLT-2i) may significantly improves COVID-19 outcomes in patients with diabetes: A systematic review, meta-analysis, and meta-regression. Diabetes Res Clin Pract 2023; 195: 110205. doi: 10.1016/j.diabres.2022.110205 PMID: 36502891
  66. Zhu Z, Zeng Q, Liu Q, Wen J, Chen G. Association of glucose-lowering drugs with outcomes in patients with diabetes before hospitalization for COVID-19. JAMA Netw Open 2022; 5(12): e2244652. doi: 10.1001/jamanetworkopen.2022.44652 PMID: 36472874
  67. Woods TC, Satou R, Miyata K, et al. Canagliflozin prevents intrarenal angiotensinogen augmentation and mitigates kidney injury and hypertension in mouse model of type 2 diabetes mellitus. Am J Nephrol 2019; 49(4): 331-42. doi: 10.1159/000499597 PMID: 30921791
  68. Burns KD, Cherney D. Renal angiotensinogen and sodium-glucose cotransporter-2 inhibition: Insights from experimental diabetic kidney disease. Am J Nephrol 2019; 49(4): 328-30. doi: 10.1159/000499598 PMID: 30921790
  69. Bosch A, Poglitsch M, Kannenkeril D, et al. Angiotensin pathways under therapy with empagliflozin in patients with chronic heart failure. ESC Heart Fail 2023; 10(3): 1635-42. doi: 10.1002/ehf2.14313 PMID: 36782339
  70. Shikuma J, Sakakura K, Sugiyama-Takahashi M, et al. Hematocrit elevation after SGLT2 inhibitor administration may be associated with the degree of proximal tubular damage. Medicine 2022; 101(42): e31122. doi: 10.1097/MD.0000000000031122 PMID: 36281104
  71. Hadadi A, Mortezazadeh M, Kolahdouzan K, Alavian G. Does recombinant human erythropoietin administration in critically ill COVID-19 patients have miraculous therapeutic effects? J Med Virol 2020; 92(7): 915-8. doi: 10.1002/jmv.25839 PMID: 32270515
  72. Al Sulaiman K, Aljuhani O, Korayem GB, et al. The impact of recombinant human erythropoietin administration in critically ill COVID-19 patients: A multicenter cohort study. Clin Appl Thromb Hemost 2023; 29: 10760296231218216. doi: 10.1177/10760296231218216 PMID: 38073058
  73. Lim S, Bae JH, Kwon HS, Nauck MA. COVID-19 and diabetes mellitus: From pathophysiology to clinical management. Nat Rev Endocrinol 2021; 17(1): 11-30. doi: 10.1038/s41574-020-00435-4 PMID: 33188364
  74. Al-kuraishy HM, Al-Gareeb AI, Al-Hamash SM, et al. Changes in the blood viscosity in patients with SARS-CoV-2 infection. Front Med 2022; 9: 876017. doi: 10.3389/fmed.2022.876017 PMID: 35783600
  75. Mazer CD, Hare GMT, Connelly PW, et al. Effect of empagliflozin on erythropoietin levels, iron stores, and red blood cell morphology in patients with type 2 diabetes mellitus and coronary artery disease. Circulation 2020; 141(8): 704-7. doi: 10.1161/CIRCULATIONAHA.119.044235 PMID: 31707794
  76. Feingold KR. The bidirectional interaction of COVID-19 infections and lipoproteins. Best Pract Res Clin Endocrinol Metab 2023; 37(4): 101751. doi: 10.1016/j.beem.2023.101751 PMID: 36894344
  77. Mink S, Saely CH, Frick M, Leiherer A, Drexel H, Fraunberger P. Association between lipid levels, anti-SARS-CoV-2 spike antibodies and COVID-19 mortality: A prospective cohort study. J Clin Med 2023; 12(15): 5068. doi: 10.3390/jcm12155068 PMID: 37568470
  78. Inagaki N, Kondo K, Yoshinari T, Kuki H. Efficacy and safety of canagliflozin alone or as add-on to other oral antihyperglycemic drugs in Japanese patients with type 2 diabetes: A 52-week open-label study. J Diabetes Investig 2015; 6(2): 210-8. doi: 10.1111/jdi.12266 PMID: 25802729
  79. Bechmann LE, Emanuelsson F, Nordestgaard BG, Benn M. SGLT2-inhibition increases total, LDL, and HDL cholesterol and lowers triglycerides: Meta-analyses of 60 randomized trials, overall and by dose, ethnicity, and drug type. Atherosclerosis 2023; 117236: 117236. doi: 10.1016/j.atherosclerosis.2023.117236 PMID: 37582673
  80. Putnam K, Shoemaker R, Yiannikouris F, Cassis LA. The renin-angiotensin system: A target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome. Am J Physiol Heart Circ Physiol 2012; 302(6): H1219-30. doi: 10.1152/ajpheart.00796.2011 PMID: 22227126
  81. Athanassiou L, Kostoglou-Athanassiou I, Nikolakopoulou S, et al. Vitamin D levels as a marker of severe SARS-CoV-2 infection. Life 2024; 14(2): 210. doi: 10.3390/life14020210 PMID: 38398719
  82. Rachman A, Rahmaniyah R, Khomeini A, Iriani A. Impact of vitamin D deficiency in relation to the clinical outcomes of hospitalized COVID-19 patients. F1000 Res 2023; 12: 394. doi: 10.12688/f1000research.132214.3 PMID: 38434628
  83. Singh A, Rastogi A, Puri GD, et al. Therapeutic high-dose vitamin D for vitamin D-deficient severe COVID-19 disease: randomized, double-blind, placebo-controlled study (SHADE-S). J Public Health 2024; fdae007. doi: 10.1093/pubmed/fdae007 PMID: 38291897
  84. Dilokpattanamongkol P, Yan C, Jayanama K, Ngamjanyaporn P, Sungkanuparph S, Rotjanapan P. Impact of vitamin D supplementation on the clinical outcomes of COVID-19 pneumonia patients: A single-center randomized controlled trial. BMC Complement Med Ther 2024; 24(1): 97. doi: 10.1186/s12906-024-04393-6 PMID: 38383361
  85. Blau JE, Bauman V, Conway EM, et al. Canagliflozin triggers the FGF23/1,25-dihydroxyvitamin D/PTH axis in healthy volunteers in a randomized crossover study. JCI Insight 2018; 3(8): e99123. doi: 10.1172/jci.insight.99123 PMID: 29669938
  86. Kwiendacz H, Nabrdalik K, Wijata AM, et al. Relationship of vitamin D deficiency to cardiovascular disease and glycemic control in patients with type 2 diabetes mellitus: The Silesia Diabetes- Heart Project. Pol Arch Int Med 2023; 133(6): 16445. doi: 10.20452/pamw.16445 PMID: 36856666
  87. Verdoia M, De Luca G. Is there an actual link between vitamin D deficiency, cardiovascular disease, and glycemic control in patients with type 2 diabetes mellitus? Pol Arch Int Med 2023; 133(6): 16516. doi: 10.20452/pamw.16516 PMID: 37351588

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