Benefit of gliflozines on atherosclerosis?

Česká verzia

Authors: Marián Mokáň; Peter Galajda
Authors place of work: I. interná klinika JLF UK a UNM, Martin
Published in the journal: Forum Diab 2021; 10(3): 207-212
Category:

Summary

Gliflozins or sodium-glucose co-transporter 2 (SGLT2) inhibitors, are the newest class of diabetic medications indicated for the treatment of type 2 diabetes mellitus. Apart from glycaemic control and low risk of hypoglycaemia, gliflozins have been shown to provide significant cardiovascular benefit. They significantly reduce risk of heart failure, as it was shown in studies EMPA-REG OUTCOME with empagliflozin, CANVAS with canagliflozin and DECLARE-TIMI-58 with dapagliflozin in subgroup of patients with high cardiovascular risk. In the study EMPRISE there were confirmed the benefit of empagliflozin not only in reduced hospitalization for heart failure but also comparable effect on reduced incidence of atherosclerotic cardiovascular events. In secondary analysis of EMPA-REG OUTCOME study with evaluation of first plus every recurrent event there were confirmed that treatment by empagliflozin is associated with reduction of incidence of myocardial infarction by 21 %, main coronary events (myocardial infarction or coronary revascularization) by 20 %, cardiovascular mortality by 38% and total mortality from every reasons by 31 %. Clinical and experimental studies suggest, that gliflozin treatment is associated with not only reduction of heart failure, but also with long term benefit an atherosclerotic cardiovascular diseases.

Keywords:

Atherosclerosis – diabetes mellitus – cardiovascular benefit – gliflozins– sodium-glucose co-transporter 2 (SGLT2) inhibitors type 2

Zdroje

1. American Diabetes Association. Cardiovascular disease and risk management: Standards of Medical Care in Diabetes – 2021. Diabetes Care 2021; 44(Suppl1): S125-S150. Dostupné z DOI: <http://dx.doi.org/10.2337/dc21-S010>.

2. Martinka E, Tkáč I, Mokáň M et al. Interdisciplinárne štandardy diagnostiky a liečby diabetes mellitus, jeho komplikácií a najvýznamnejších sprievodných ochorení. Forum Diab 2018; 7(2 Suppl1): 5–153.

3. Vallon V, Thomson SC. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia 2017; 60(2): 215–225. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–016–4157–3>.

4. Mokáň M, Galajda P. Perspektívy liečby diabetes mellitus inhibítormi sodíko-glukózového kotransportéra 2. Diab Obez 2018; 18(35):43–50.

5. Zinman B, Wanner C, Lachin JM et al. [EMPAREG-OUTCOME Investigators]. Empagliflozine, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373(22): 2117–2128. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1504720>.

6. Packer M, Anker SD, Butler J et al. Cardiovascular and renal outcomes with empaggliflozin in heart failure. N Engl J Med 2020; 383(15): 1413–1424. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa2022190>.

7. Neal B, Perkovic V, Mahaffey KW et al. [CANVAS Program Collaborative Group]. Canagliflozine and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377(7): 644–657. Dostupné z DOI:<http://dx.doi.org/10.1056/NEJMoa1611925>.

8. Wiviott SD, Raz I, Bonaca MP et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019; 380(4): 347–357. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1812389>.

9. Cavender MA, Norhammar A, Birkeland KI et al. [CVD-REAL Investigators and Study Group]. SGLT-2 inhibitors and cardiovascular risk: An analysis of CVD-REAL. J Am Coll Cardiol 2018; 71(22): 2497–2506. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2018.01.085>.

10. Patorno E, Pawar A, Franklin JM et al. Empagliflozin and the risk of heart failure hospitalization in routine clinical care: a first analysis from the empagliflozin comparative effectiveness and safety (EMPRISE) Study. Circulation 2019; 139(25): 2822–2830. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.118.039177>.

11. Schernthaner G, Karasik A, Abraitienė A et al. Evidence from routine clinical practice: EMPRISE provides a new perspective on CVOTs Cardiovasc Diabetol 2019; 18(1): 115. Dostupné z DOI: <http://dx.doi.org/10.1186/s12933–019–0920–3>.

12. Martinka E. Štúdia EMPRISE: empagliflozín redukuje počet hospitalizácií pre srdcové zlyhávanie. Potvrdenie z bežnej klinickej praxe. Forum Diab 2019; 8(3): 193–199.

13. Mokáň M, Galajda P. Gliflozíny a srdce – analýzy štúdie EMPRISE. Forum Diab 2020; 9(2): 115–119.

14. Patorno E, Pawar A, Franklin J et al. Cardiovascular effectiveness of empagliflozin compared to DPP4 inhibitors and to GLP1 receptor agonists: Interim analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) study. AHA 2019 Scientific Session. Circulation 2019; 140(Suppl 1): A11928.

15. Patorno E, Pawar A, Bessette LG et al. Cardiovascular outcomes in older adults initiating Empagliflozin vs. DPP4 inhibitors and GLP1 receptor agonists: a subgroup analysis from the EMPRISE study. Diabetes 2020; 69(Suppl 1): 133-LB. Dostupné z DOI: <https://doi.org/10.2337/db20–133-LB>.

16. Longato E, Di Camillo B, Sparacino G et al. Cardiovascular outcomes of type 2 diabetic patients treated with SGLT-2 inhibitors versus GLP-1 receptor agonists in real-life. BMJ Open Diab Res Care 2020; 8(1): e001451. Dostupné z DOI: <http://dx.doi.org/10.1136/bmjdrc-2020–001451>.

17. McGuire DK, Zinman B, Inzucchi SE et al. Effects of empagliflozin on first and recurrent clinical events in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a secondary analysis of the EMPA-REG OUTCOME trial. Lancet Diabetes Endocrinol 2020;

8(12): 949–959. Dostupné z DOI: <http://dx.doi.org/10.1016/S2213–8587(20)30344–2>.

18. Staels B. Cardiovascular protection by sodium glucose cotransporter 2 inhibitors: potential mechanisms. Am J Cardiol 2017; 120(1S): S28-S36. Dostupné z DOI: <http://dx.doi.org/10.1016/j.amjcard.2017.05.013>.

19. Verma S, McMurray JJV. SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia 2018; 61(10): 2108–2117. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–018–4670–7>.

20. Lopaschuk GD, Verma S. Mechanisms of cardiovascular benefits of sodium glucose co-transporter 2 (SGLT2) inhibitors: A State-of-the-Art Review. JACC Basic Transl Sci 2020; 5(6): 632–644. Dostupné z DOI:<http://dx.doi.org/10.1016/j.jacbts.2020.02.004>.

21. Sanchez Garcia A, Simental-Mendia M, Millan-Alanis JM et al. Effect of sodium-glucose co-transporter 2 inhibitors on lipid profile: A systematic review and meta-analysis of 48 randomized controlled trials. Pharmacol Res 2020; 160: 105068. Dostupné z DOI: <http://dx.doi.org/10.1016/j.phrs.2020.105068>.

22. Kern M, Kloting N, Mark M et al. The SGLT2 inhibitor empagliflozin improves insulin sensitivity in db/db mice both as monotherapy and in combination with linagliptin. Metabolism 2016; 65(2): 114–123. Dostupné z DOI: <http://dx.doi.org/10.1016/j.metabol.2015.10.010>.

23. Filippas-Ntekouan S, Tsimihodimos V, Filippatos T et al. SGLT-2 inhibitors: pharmacokinetics characteristics and effects on lipids. Expert Opin Drug Metab Toxicol 2018; 14(11): 1113–1121. Dostupné z DOI: <http://dx.doi.org/10.1080/17425255.2018.1541348>.

24. Briand F, Mayouux E, Brosseasu E et al. Empagliflozin, via switching metabolism toward lipid utilization, moderately increases LDL cholesterol levels through reduced LDL catabolism. Diabetes 2016; 65(7): 2032–2038. Dostupné z DOI: <http://dx.doi.org/10.2337/db16–0049>.

25. 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): 1801–1808. Dostupné z DOI: <http://dx.doi.org/10.2337/dc18–0165>.

26. Scheen AJ. Effect of sodium-glucose cotransporter type 2 inhibitors on liver fat in patients with type 2 diabetes: hepatic beyond cardiovascular and renal protection? Ann Transl Med 2018; 6(Suppl 1): S68. Dostupné z DOI: <http://dx.doi.org/10.21037/atm.2018.10.39>.

27. Xu L, Nagata N, Nagashimada M et al. SGLT2 inhibition by empagliflozin promotes fat utilization and browning and attenuates inflammation and insulin resistance by polarizing M2 macrophages in diet-induced obese mice. EBioMedicine 2017; 20: 137–149. Dostupné z DOI:<http://dx.doi.org/10.1016/j.ebiom.2017.05.028>.

28. Xu L, Ota T. Emerging roles of SGLT2 inhibitors in obesity and insulin resistance: Focus on fat browning and macrophage polarization. Adipocyte 2018; 7(2): 121–128. Dostupné z DOI: <http://dx.doi.org/10.1080/21623945.2017.1413516>.

29. Bonnet F, Scheen AJ. Effects of SGLT2 inhibitors on systemic and tissue low-grade inflammation: The potential contribution to diabetes complications and cardiovascular disease. Diabetes Metab 2018; 44(6): 457–464. Dostupné z DOI: <http://dx.doi.org/10.1016/j.diabet.2018.09.005>.

30. Kang Y, Zhan F, He M et al. Anti-inflammatory effects of sodium-glucose co-transporter 2 inhibitors on atherosclerosis. Vascul Pharmacol 2020; 133–134: 106779. Dostupné z DOI: <http://dx.doi.org/10.1016/j.vph.2020.106779>.

31. Terasaki M, Hiromura M, Mori Y et al. Amelioration of hyperglycemia with a sodium-glucose cotransporter 2 inhibitor prevents macrophage-driven atherosclerosis through macrophage foam cell formation suppression in type 1 and type 2 diabetic mice. PLoS One 2015; 10(11): e143396. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0143396>.

32. Leng W, Ouyang X, Lei X et al. The SGLT-2 inhibitor Dapagliflozin has a therapeutic effect on atherosclerosis in diabetic ApoE−/− mice. Mediators Inflamm 2016; 2016: 6305735. Dostupné z DOI: <http://dx.doi.org/10.1155/2016/6305735>.

33. Nasiri-Ansari N, Dimitriadis G, Agriogannis G et al. Canagliflozin attenuates the progression of atherosclerosis and inflammation process in APOE knockout mice. Cardiovasc Diabetol 2018; 17(1): 106. Dostupné z DOI: <http://dx.doi.org/10.1186/s12933–018–0749–1>.

34. Han JH, Oh TJ, Lee G et al. The beneficial effects of empagliflozin, an SGLT2 inhibitor, on atherosclerosis in ApoE -/- mice fed a western diet. Diabetologia 2017; 60(2): 364–376. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–016–4158–2.

35. Dimitriadis GK, Nasiri-Ansari N, Agrogiannis G et al. Empagliflozin improves primary haemodynamic parameters and attenuates the development of atherosclerosis in high fat diet fed APOE knockout mice. Mol Cel Endocrinol 2019; 494: 110487. Dostupné z DOI: <http://dx.doi.org/10.1016/j.mce.2019.110487>.

36. Kim SR, Lee SG, Kim SH et al. SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease. Nat Commun 2020; 11(1): Dostupné z DOI: 2127. <http://dx.doi.org/10.1038/s41467–020–15983–6>.

37. Lee SG, Lee SJ, Lee JJ et al. Anti-inflammatory effect for atherosclerosis progression by sodium-glucose cotransporter 2 (SGLT-2) inhibitor in a normoglycemic rabbit model. Korean Circ J 2020; 50(5): 443–457. Dostupné z DOI: <http://dx.doi.org/10.4070/kcj.2019.0296>.

38. Martinka E, Mokáň M, Rašlová K, Tkáč I, Schroner Z, Galajda P (eds) et al. Interdisciplinárne odporúčania pre diagnostiku a liečbu diabetes mellitus, jeho komplikácií a najvýznamnejších sprievodných ochorení – 2021. Forum Diab 2021; 10(Suppl 2).