Antidiabetic treatment in prevention of atherosclerosis: last decade


Authors: Emil Martinka 1,2
Authors‘ workplace: Národný endokrinologický a diabetologický ústav, n. o., Ľubochňa 1;  Fakulta zdravotníckych vied Piešťany, Univerzita Sv. Cyrila a Metoda, Trnava 2
Published in: Forum Diab 2021; 10(Suplement 1): 16-27
Category:

Overview

In the last five years, the results of several studies aimed at testing the cardiovascular (CV) safety (so-called “CVOT” studies) of newer antidiabetic drug users have been published, which have attracted special attention and become one of the most important in diabetology. Indeed, they have shown that drugs from the group of SGLT-2 cotransport inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1-RA) are not only cardiovascular safe, but their addition to treatment is associated with a significant reduction in cardiovascular and renal morbidity and mortality even with previously complexive cardioprotective treatment. In the review article, we analyze the results of the most important randomized controlled trials, as well as a study from real practice, as well as the implementation of these findings into therapeutic recommendations.

Keywords:

antidiabetic treatment – Atherosclerosis – cardiovascular diseases – dipeptidyl peptidase 4 inhibitors – GLP1 receptor agonists – SGLT-2 cotransport inhibitors


Sources
  1. Almutairi M, Al Batran R, Ussher JR. Glucagon-like peptide-1 receptor action in the vasculature. Peptides 2019; 111: 26–32. Dostupné z DOI: <http://dx.doi.org/10.1016/j.peptides.2018.09.002>.
  2. [American Diabetes Association]. 9. Pharmacologic approaches to glycemic treatment: Standards of medical care in diabetes 2021. Diabetes Care 2021; 44(Suppl 1): S111-S124. Dostupné z DOI: <http://dx.doi.org/10.2337/dc21-S009>.
  3. Aragón-Herrera A, Feijóo-Bandín S, Otero Santiago M et al. Empagliflozin reduces the levels of CD36 and cardiotoxic lipids while improving autophagy in the hearts of Zucker diabetic fatty rats. Biochem Pharmacol 2019; 170: 113677. Dostupné z DOI: <http://dx.doi.org/10.1016/j.bcp.2019.113677>.
  4. Aroor AR, Sowers JR, Jia G et al. Pleiotropic effects of the dipeptidylpeptidase-4 inhibitors on the cardiovascular system. Am J Physiol Heart Circ Physiol 2014; 307(4): H477–492. Dostupné z DOI: <http://dx.doi.org/10.1152/ajpheart.00209.2014>.
  5. Baggio LL, Drucker DJ. Biology of Incretins: GLP-1 and GIP. Gastroenterol 2007; 132(6): 2131–2157. Dostupné z DOI: Dostupné z DOI: <http://dx.doi.org/10.1053/j.gastro.2007.03.054>.
  6. Bosch A, Ott C, Jung S et al. How does empagliflozin improve arterial stiffness in patients with type 2 diabetes mellitus? Sub analysis of a clinical trial. Cardiovasc Diabetol 2019; 18(1): 44. Dostupné z DOI: <http://dx.doi.org/10.1186/s12933–019–0839–8>.
  7. Butler J, Packer M, Anker SD et al. Empagliflozin for the treatment of chronic heart failure and a reduced ejection fraction in patients with and without diabetes: new results of the EMPEROR-Reduced trial. J Am Coll Cardiol 2021; 77(11): 1381–1392. Dostupné z DOI: <https:// doi 10.1016/j.jacc.2021.01.033>.
  8. Cosentino F, Grant PJ, Aboyans V et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 2020;41(2): 255–323. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehz486>.
  9. Covie MR, Fisher M. SGLT2 inhibitors: mechanisms of cardiovascular benefit beyond glycaemic control. Nat Rev Cardiol 2020; 17(12): 761–772. Dostupné z DOI: <http://dx.doi.org/10.1038/s41569–020–0406–8>.
  10. Daacke I, Kandaswamy P, Tebboth A et al. Impact of Empagliflozin (Jardiance) to the NHS: estimation of budget and event impact based on empa-reg outcome data. Value Health 2016;19(7): PA668. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jval.2016.09.1852>.
  11. Davies MJ, D’Alessio DA, Fradkin J et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2018; 2018(61): 2461–2498. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–018–4729–5>.
  12. Ferrannini E, Mark M, Mayoux E. CV Protection in the EMPA-REG OUTCOME Trial: A „Thrifty Substrate“ Hypothesis. Diabetes Care 2016; 39(7): 1108–1114. Dostupné z DOI: <http://dx.doi.org/10.2337/dc16–0330>.
  13. Fitchett D, Zinman B, Wanner C, Lachin JM, Hantel S, Salsali A, et al. Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME® trial. Eur Heart J 2016; 37(19): 1526–1534. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehv728>.
  14. Galwitz B, Rosenstock J, Rauch T et al. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet 2012; 380(9840): 475–483. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(12)60691–6>.
  15. Gerstein HC, Colhoun HM, Dagenais GR et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet 2019; 394(10193): 121–130. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(19)31149–3>.
  16. Gerstein HC, Colhoun HM, Dagenais GR et al. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. Lancet 2019; 394(10193): 131–138. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(19)31150-X>.
  17. Hallow KM, Helmlinger G, Greasley PJ et al. Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis. Diabetes Obes Metab 2018; 20(3): 479–487. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.13126>.
  18. Heerspink HJL, Karasik A, Thuresson M et al. Kidney outcomes associated with use of SGLT2 inhibitors in real-world clinical practice (CVD-REAL 3): a multinational observational cohort study. Lancet Diabetes Endocrinol 2020; 8(1): 27–35. Dostupné z DOI: <http://dx.doi.org/10.1016/S2213–8587(19)30384–5>.
  19. Heerspink HJL, Stefánsson BV, Correa-Rotter R et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med 2020; 383(15): 1436–1446. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa2024816>.
  20. 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): 1519–1529. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(18)32261-X>.
  21. Holman RR, Bethel MA, Mentz RJ et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2017; 377(13): 1228–1239. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1612917>.
  22. Hramiak I, Vilsbøll T, Gumprecht J et al. Semaglutide treatment and renal function in the SUSTAIN 6 trial. Can J Diabetes 2018; 42(5 Suppl): S42. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jcjd.2018.08.126>.
  23. Husain M, Birkenfeld AL, Donsmark M, Dungan K, Eliaschewitz FG, Franco DR, et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2019; 381(9):841–851. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1901118>.
  24. Chiasson JL, Gomis R, Hanefeld M et al. The STOP-NIDDM Trial: an international study on the efficacy of an alpha-glucosidase inhibitor to prevent type 2 diabetes in a population with impaired glucose tolerance: rationale, design, and preliminary screening data. Study to Prevent Non-Insulin-Dependent Diabetes Mellitus. Diabetes Care 1998; 21(10): 1720–1725. Dostupné z DOI: <http://dx.doi.org/10.2337/diacare.21.10.1720>.
  25. Inzucchi SE, Zinman B, Wanner C et al. Empagliflozin Reduces the Total Burden of All-cause Hospitalizations. American Diabetes Association (ADA) 80th Scientific Sessions 2020, June 12–16. Virtual Meeting. 131-LB. Dostupné z WWW: <https://www.easd.org/virtualmeeting/home.html%20#!resources/43091>.
  26. Klein LJ, VisserFC. The effect of insulin on the heart. Net Heart J 2010; 18(4): 197–201. Dostupné z DOI: <http://dx.doi.org/10.1007/BF03091761>.
  27. Kosiborod M, Cavender MA, Fu AZ et al. Lower risk of heart failure and death in patients initiated on sodium-glucose cotransporter-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors) Circulation 2017; 136(3): 249–259. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.117.029190>.
  28. Kosiborod M, Lam CSP, Kohsaka S et al. Cardiovascular events associated with SGLT-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL 2 study. J Am Coll Cardiol 2018; 71(23): 2628–2639. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2018.03.009>.
  29. Koyani CN, Plastira I, Sourij H et al. Empagliflozin protects heart from inflammation and energy depletion via AMPK activation. Pharmacol Res 2020; 158: 104870. Dostupné z DOI: <http://dx.doi.org/10.1016/j.phrs.2020.104870>.
  30. 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.
  31. Makdishi A, Ghanim H, Vora M et al. Sitagliptin exerts an antinflammatory action. J Clin Endocrinol Metab. 2012; 97(9): 3333–3341. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2012–1544>.
  32. Mann JFE, Ørsted DD, Brown-Frandsen K et al. Liraglutide and renal outcomes in type 2 diabetes. N Engl J Med 2017; 377(9): 839–848. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1616011>.
  33. Marso SP, Daniels GH, Brown-Frandsen K et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016; 375(4): 311–322. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1603827>.
  34. Marso SP, Bain SC, Consoli A et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016;375(19): 1834–1844. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1607141>.
  35. Matthews DR Dejager S Ahren B et al. Vildagliptin add-on to metformin produces similar efficacy and reduced hypoglycaemic risk compared with glimepiride, with no weight gain: results from a 2-year study. Diabetes Obes Metab 2010; 12(9): 780–789. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1463–1326.2010.01233.x>.
  36. Mazzone PJ, Rai H, Beukemann M, Xu M,Jain AK, Sasidhar M. The effect of metformin and thiazolidinedione use on lung cancer in diabetics. BMC Cancer 2012; 12: 410. Dostupné z DOI: <http://dx.doi.org/10.1186/1471–2407–12–410>.
  37. 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>.
  38. McMurray JJ, Solomon SD, Inzucchi SE et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med 2019; 381(21): 1995–2008. Dostupné z DOI: <http://dx.doi.org/10.1056/ NEJMoa1911303>.
  39. McMurray JJV, Solomon SD, Inzucchi SE et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 2019; 381(21): 1995–2008. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1911303>.
  40. Monami M, Genovese S, Mannucci E. Cardiovascular Safety Of Sulfonylureas: A Meta-Analysis Of Randomised Clinical Trials. Diabetes Obes Metab 2013; 15(10): 938–953. Dostupné z DOI: <http://doi: 10.1111/dom.12116>.
  41. Monteiro P, Bergenstal RM, Toural E et al. Efficacy and safety of empagliflozin in older patients in the EMPA-REG OUTCOME® trial. Age Ageing 2019; 48(6): 859–866. Dostupné z DOI: <http://dx.doi.org/10.1093/ageing/afz096>.
  42. Mosenzon O, Wiviott SD, Cahn A et al. Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE-TIMI 58 randomised trial. Lancet Diabetes Endocrinol 2019; 7(8): 606–617. Dostupné z DOI: <http://dx.doi.org/10.1016/S2213–8587(19)30180–9>.
  43. Muskiet MH, Tonneijck L, Huang Y et al. Lixisenatide and renal outcomes in patients with type 2 diabetes and acute coronary syndrome: an exploratory analysis of the ELIXA randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 2018; 6(11): 859–869. Dostupné z DOI: <https://doi.org/10.1016/S2213–8587(18)30268–7>.
  44. Najafzadeh M, Pawar A, Déruaz-Luyet A et al. PDB128 Reduced healthcare utilization in patients using empagliflozin: an interim analysis from the empagliflozin comparative effectiveness and safety (EMPRISE) study. Value Health 2019; 22(Suppl 2): S161. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jval.2019.04.675>.
  45. Nagahisa T, Saisho Y. Cardiorenal protection: potential of SGLT2 inhibitors and GLP-1 receptor agonists in the treatment of type 2 diabetes. Diabetes Ther 2019; 10(5): 1733–1752. Dostupné z DOI: <http://dx.doi.org/10.1007/s13300–019–00680–5>.
  46. Nauck MA, Ouaghlidi AE. The therapeutic actions of DPP-IV inhibition are not mediated by glucagon-like peptide-1 Diabetologia. 2005; 48(4): 608–611. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–005–1704–8>.
  47. Packer M, Anker SD, Butler J et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med 2020; 383(15): 1413–1424. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa2022190>.
  48. Paolisso G, Monami M, Marfella R et al. Dipeptidyl Peptidase-4 Inhibitors in the Elderly: More Benefits or Risks? Adv Ther 2012; 29(3): 218–233. Dostupné z DOI: <http://dx.doi.org/10.1007/s12325–012–0008-x>.
  49. Patorno E, Pawar A, Bessette LG et al. Cardiovascular outcomes in older adults initiating Empagliflozin vs DPP-4 inhibitors and GLP-1 receptor agonists: a subgroup analysis from the EMPRISE study. American Diabetes Association (ADA) 80th Scientific Sessions 2020, June 12–16. Virtual Meeting. 133-LB. Dostupné z WWW: <https://plan.core-apps.com/tristar_ada20/abstract/ff32b460–6aeb-47be-87a4–99cd64ce1381>.
  50. Patorno E, Pawar A, Lily G et al. Effectiveness and safety of empagliflozin in routine care patients: interim results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study. American Diabetes Association (ADA) 80th Scientific Sessions 2020, June 12–16. Virtual Meeting. 134-LB. Dostupné z DOI: <https://doi.org/10.2337/db20–134-LB>.
  51. 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 EMPRISE Study. Circulation 2019; 139(25): 2822–2830. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.118.039177>.
  52. Pasternak B, Ueda P, Eliasson B et al. Use of sodium glucose cotransporter 2 inhibitors and risk of major cardiovascular events and heart failure: Scandinavian register based cohort study. BMJ 2019; 366: l4772. Dostupné z DOI: <http://dx.doi.org/10.1136/bmj.l4772>.
  53. Pasternak B, Wintzell V, Melbye M et al. Use of sodium-glucose co-transporter 2 inhibitors and risk of serious renal events: Scandinavian cohort study. BMJ. 2020; 369: m1186. Dostupné z DOI: <http://dx.doi.org/10.1136/bmj.m1186>.
  54. Pawar A, Patorno E, Deruaz-Luyet A et al. Health-care costs and medication burden in routine care initiators of empagliflozin: a first analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) study. Diabetes 2019; 68(Suppl 1): 1193-P. Dostupné z DOI: <http://dx.doi.org/10.2337/db19–1193-P>.
  55. Pawar A, Patorno E, Deruaz-Luyet A et al. Reduced healthcare utilization in routine care initiators of empagliflozin with and without heart failure: interim analysis from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study. Eur Heart J 2019; 40(Suppl 1): ehz746.0181. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehz746.0181>.
  56. Pawar A, Patorno E, Déruaz-Luyet A et al. Comparative healthcare costs and medication burden in real-world patients augmenting metformin monotherapy with empagliflozin from the empagliflozin comparative effectiveness and safety (EMPRISE) study. Value Health 2019; 22(Supp 2): S161. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jval.2019.04.673>.
  57. Perkovic V, Jardine MJ, Neal B et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019; 380(24): 2295–2306. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1811744>.
  58. Perkovic V, de Zeeuw D, Mahaffey KW et al. Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials. Lancet Diabetes Endocrinol 2018; 6(9): 691–704. <http://dx.doi.org/10.1016/S2213–8587(18)30141–4>.
  59. Pfeffer MA, Claggett B, Diaz R et al. [ELIXA Investigators]. Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome. N Engl J Med 2015; 373(23): 2247–2257. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1509225>.
  60. Rosenstock J, Perkovic V, Johansen OE et al. Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk The CARMELINA Randomized Clinical Trial. JAMA 2019; 321(1): 69–79. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.2018.18269>.
  61. Scirica BM, Bhatt DL, Braunwald E et al. Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus. N Engl J Med 2013; 369(14): 1317–26. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1307684>.
  62. Seck T, Nauck M, Sheng D et al. Safety and efficacy of treatment with sitagliptin or glipizide in patients with type 2 diabetes inadequately controlled on metformin: a 2-year study. Int J Clin Pract 2010; 64(5): 562–576. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1742–1241.2010.02353.x>.
  63. Seferović PM, Fragasso G, Petrie M et al. Sodium glucose co-transporter-2 inhibitors in heart failure: beyond glycaemic control. The Position Paper of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2020; 22(9): 1495–1503. <http://dx.doi.org/10.1002/ejhf.1954>.
  64. Shehadeh N, Raz I, Nakhleh A. Cardiovascular benefit in the limelight: shifting type 2 diabetes treatment paradigm towards early combination therapy in patients with overt cardiovascular disease. Cardiovasc Diabetol 2018; 17(1): 117. Dostupné z DOI: <http://dx.doi.org/10.1186/s12933–018–0760–6>.
  65. Scheen AJ. SGLT2 inhibitors: benefit/risk balance. Curr Diab Rep 2016; 16(10): 92. Dostupné z DOI: <http://dx.doi.org/10.1007/s11892–016–0789–4>.
  66. Schernthaner G, Lehmann R, Prázný M et al. Translating recent results from the Cardiovascular Outcomes Trials into clinical practice: recommendations from the Central and Eastern European Diabetes Expert Group (CEEDEG). Cardiovasc Diabetol 2017; 16(1): 137. Dostupné z DOI: <http://dx.doi.org/10.1186/s12933–017–0622–7>.
  67. Simpson SH, Lee J, Choi S et al. Mortality risk among sulfonylureas: a systematic review and network meta-analysis. Lancet Diabetes Endocrinol 2015; 3(1): 43–51. Dostupné z DOI: <http://dx.doi.org/10.1016/S2213–8587(14)70213-X>.
  68. Thomas MC, Cherney DZ. The actions of SGLT2 inhibitors on metabolism, renal function and blood pressure. Diabetologia 2018; 61(10): 2098–2107. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–018–4669–0>.
  69. Tkac I, Raz I. Combined Analysis of Three Large Interventional Trials With Gliptins Indicates Increased Incidence of Acute Pancreatitis in Patients With Type 2 Diabetes. Diabetes Care 2017; 40(2): 284–286. Dostupné z DOI: <http://dx.doi.org/10.2337/dc15–1707>.
  70. Tsalamandris S, Antonopoulos AS, Oikonomou E et al. The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives. Eur Cardiol 2019; 14(1): 50–59. Dostupné z DOI: <http://dx.doi.org/10.15420/ecr.2018.33.1>.
  71. Uthman L, Baartscheer A, Bleijlevens B et al. Class effects of SGLT2 inhibitors in mouse cardiomyocytes and hearts: inhibition of Na+/H+ exchanger, lowering of cytosolic Na+ and vasodilation. Diabetologia 2018; 61(3): 722–726. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–017–4509–7>.
  72. Vallon V. The mechanisms and therapeutic potential of SGLT2 inhibitors in diabetes mellitus. Annu Rev Med 2015; 66: 255–270. Dostupné z DOI: <http://dx.doi.org/10.1146/annurev-med-051013–110046>.
  73. Verma S, Leiter LA, Sharma A et al. How early after treatment initiation are the CV benefits of empagliflozin apparent? A post hoc analysis of EMPA-REG OUTCOME. Diabetes 2020; 69(Suppl 1): 28-OR. Dostupné z DOI: < https://doi.org/10.2337/db20–28-OR>.
  74. Wanner C, Inzucchi SE, Lachin JM et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 2016; 375(4): 323–334. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1515920>.
  75. 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>.
  76. Yin WL, Bain SC, Min T. The effect of glucagon-like peptide-1 receptor agonists on renal outcomes in type 2 diabetes. Diabetes Ther 2020; 11(4): 835–844. Dostupné z DOI: <http://dx.doi.org/10.1007/s13300–020–00798-x>.
  77. Zinman B, Wanner C, Lachin JM et al. Empagliflozin, 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>.
Labels
Diabetology Endocrinology Internal medicine
Login
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account