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A consensual therapeutic recommendation for type 2 diabetes mellitus by the Slovak Diabetes Society (2018)


Authors: Emil Martinka;  Vladimír Uličiansky;  Marián Mokáň;  Ivan Tkáč;  Peter Galajda;  Silvia Dókušová;  Zbynek Schroner *
Authors‘ workplace: Slovenská diabetologická spoločnosť Slovenskej lekárskej spoločnosti
Published in: Vnitř Lék 2018; 64(4): 405-426
Category: Guidelines

*v spolupráci s členmi Slovenskej diabetologickej spoločnosti

Overview

Type 2 diabetes mellitus is a heterogeneous medical condition involving multiple pathophysiological mechanisms. Its successful treatment requires an individualized approach and frequently combined therapy with utilizing its effect on multiple levels. Current possibilities enable the employment of such procedures to an incomparably greater extent than before. The effects of different classes of oral antidiabetic drugs on the reduction of glycemia and HbA1c is mutually comparable. However differences are observed in the proportions of patients who met the required criteria, regarding the increase in weight, incidence of hypoglycemia as well as the effect on cardiovascular, renal or oncologic morbidity and mortality, and severity of specific adverse effects, potential risks and contraindications. The presented text provides the reader with the information about the Consensual therapeutic algorithm for the treatment of type 2 diabetes mellitus in compliance with SPC, the ADA/EASD amended indicative limitations and recommendations, formulated by the Committee of the Slovak Diabetes Society.

Key words:
biguanides – gliflozins – gliptins – glitazones – GLP-1-receptor agonists – insulin – sulfonylurea


Sources

1. Garber AJ, Abrahamson MJ, Barzilay JI et al. AACE/ACE comprehensive diabetes management algorithm 2015. Endocrine Practice 2015; 21(4): 438–447. Dostupné z DOI: <http://dx.doi.org/10.4158/EP15693.CS>.

2. American Diabetes Association. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetesd 2018. Diabetes Care 2018; 41(Suppl 1): S73-S85. Dostupné z DOI: <https://doi.org/10.2337/dc18-S008>.

3. Baartscheer A, Schumacher CA, Wüst RC et al. Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+/H+ exchanger in rats and rabbits. Diabetologia, 2017; 60(3): 568–573. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–016–4134-x>.

4. Booth G, Lipscombe L, Butalia S et al. [Canadian Diabetes Association Clinical Practice Guidelines Expert Committee]. Pharmacologic Management of Type 2 Diabetes: 2016 Interim Update. Can J Diabetes. 2016; 40(6): 484–486. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jcjd.2016.09.003>. Erratum in Erratum to „Pharmacologic Management of Type 2 Diabetes: 2016 Interim Update“: Canadian Journal of Diabetes 2016; 40:484–486. [Can J Diabetes. 2017].

5. Gerstein HC, Miller ME, Byington RP et al. [Action to Control Cardiovascular Risk in Diabetes Study Group]. Effect of intensive glucose lowering in patients with type 2 diabetes. N Engl J Med 2008; 358(24): 2545–2559. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa0802743>.

6. Patel A, MacMahon S, Chalmers J et al. [The ADVANCE Collaborative Group]. Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2008; 358(24): 2560–2572. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa0802987>.

7. Billings LK, Doshi A, Gouet D et al. Efficacy and Safety of Insulin Degludec/Liraglutide (IDegLira) vs Basal–bolus Therapy in Patients with Type 2 Diabetes (T2D): DUAL VII Trial (NCT02420262). Oral presentation 136-OR, presented at the 77th Annual Scientific Sessions of the American Diabetes Association (ADA), San Diego, USA. 10 June 2017.

8. Bode BW, Buse JB, Fisher M et al. Insulin degludec improves glycaemic control with lower nocturnal hypoglycaemia risk than insulin glargine in basal-bolus treatment with mealtime insulin aspart in Type 1 diabetes (BEGIN(®) Basal-Bolus Type 1): 2-year results of a randomized clinical trial. Diabet Med 2013; 30(11): 1293–1297. Dostupné z DOI: <http://dx.doi.org/10.1111/dme.12243>.

9. Bonds DE, Miller ME, Bergenstal RM et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ 2010; 340: b4909. Dostupné z DOI: <http://dx.doi.org/10.1136/bmj.b4909>.

10. Dandona P1, Aljada A, Mohanty P. The anti-inflammatory and potential anti-atherogenic effect of insulin: a new paradigm. Diabetologia 2002; 45(6): 924–930. Dostupné z DOI: <http://dx.doi.org/10.1007/ s00125–001–0766–5>.

11. Dormandy JA, Charbonnel B, Eckland DJ et al. [PROactive investigators]. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macro- Vascular Events): a randomised controlled trial. Lancet 2005; 366(9493): 1279–1289. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(05)67528–9>.

12. FDA Drug Safety Communication: FDA strengthens kidney warnings for diabetes medicines canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR). Dostupné z DOI: <http://www.fda.gov/Drugs/DrugSafety/ucm505860.htm>.

13. 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>.

14. Galajda P, Martinka E, Mokán M et al. Endothelial markers in diabetes mellitus. Thromb Res 1997; 85(1): 63–65.

15. Gerstein HC, Bosch J, Dagenais GR et al. [Origin Trial Investigators]. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 2012; 367(4): 319–328. Dostupné z DOI: <http://doi: 10.1056/NEJMoa1203858>.

16. Green JB, Bethel MA, Armstrong PW et al. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2015; 373(3): 232–242. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1501352>. Erratum in Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. [N Engl J Med. 2015].

17. Hanefeld M, Bramlage P. Insulin use early in the course of type 2 diabetes mellitus: the ORIGIN trial. Curr Diab Rep 2013; 13(3): 342–349. Dostupné z DOI: <http://dx.doi.org/10.1007/s11892–013–0366-z>.

18. Hanefeld M, Monnier L, Schnell O et al. Early Treatment with Basal Insulin Glargine in People with Type 2 Diabetes: Lessons from ORIGIN and Other Cardiovascular Trials. Diabetes Ther 2016; 7(2):187–201. Dostupné z DOI: <http://dx.doi.org/10.1007/s13300–016–0153–3>.

19. Harrison LB, Adams-Huet B, Raskin P et al. b-cell function preservation after 3,5 years of intensive diabetes therapy. Diabetes Care 2012; 35(7): 1406–1412. Dostupné z DOI: <http://dx.doi.org/10.2337/ dc11–2170>.

20. Holden SE, Jenkins-Jones S, Morgan CL et al. Glucose-lowering with exogenous insulin monotherapy in type 2 diabetes: dose association with all-cause mortality, cardiovascular events and cancer. Diabetes Obes Metab 2015; 17(4): 350–362. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.12412>.

21. Holman RR, Paul SK, Bethel MA et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008; 359(15)1577–89. Dostupné z DOI: <http://dx.doi.org/1056/NEJMoa0806470>.

22. Holman RR, Bethel MA, Mentz RJ et al. [EXSCEL Study Group]. 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>.

23. Cherney DZ, Perkins BA, Soleymanlou N et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation 2014; 129(5): 587–597. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.113.005081>.

24. Chon S, Oh S, Kim SW et al. The Effect of Early Insulin Therapy on Pancreatic β-Cell Function and Long-Term Glycemic Control in Newly Diagnosed Type 2 Diabetic Patients. Korean J Intern Med 2010; 25(3): 273–281. Dostupné z DOI: <http://dx.doi.org/10.3904/ kjim.2010.25.3.273>.

25. Inzucchi SE, Bergenstal RM, Buse J Bet al. Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient-Centered Approach: Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015; 38(1):140–149. Dostupné z DOI: <http://dx.doi.org/10.2337/dc14–2441>.

26. Jones S, Benroubi M, Castell C et al. Characteristics of patients with type 2 diabetes mellitus initiating insulin therapy: baseline data from the INSTIGATE study. Curr Med Res Opin 2009; 25(3): 691–700. Dostupné z DOI: <http://dx.doi.org/10.1185/03007990902739669>.

27. King P, Peacock I, Donnelly R.The UK Prospective Diabetes Study (UKPDS): clinical and therapeutic implications for type 2 diabetes Br J Clin Pharmacol 1999; 48(5): 643–648.

28. Khunti K, Wolden ML, Thorsted BL et al. Clinical inertia in people with type 2 diabetes: a retrospective cohort study of more than 80,000 people. Diabetes Care 2013; 36(11): 3411–3417. Dostupné z DOI: <http://dx.doi.org/10.2337/dc13–0331>.

29. 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>.

30. Kramer CK, Zinman B, Choi H et al. Predictors of sustained drug-free diabetes remission over 48 weeks following short-term intensive insulin therapy in early type 2 diabetes. BMJ Open Diabetes Res Care 2016; 4(1):e000270. Dostupné z DOI: <http://dx.doi.org/10.1136/bmjdrc-2016–000270>.

31. Martinka E. NEFRITI. Dostupné z WWW: <http://dia.euni.sk/category/167-komplikacie-diabetes-mellitus/181-mikrovaskularne-komplikacie/article/2002-nefriti?bid=3>.

32. Martinka E, Pontuch P, Mišániková M et al. Výskyt diabetickej nefropatie v populácii pacientov s diabetes mellitus na Slovenku: Výsledky prieskumu NEFRITRI. Forum Diab 2015; 4(3): 198–207.

33. Martinka E. Efektivita a bezpečnosť pridania prandiálneho inzulínu glulizínu u pacientov s diabetom mellitom 2. typu nedostatočne kontrolovaných bazálnym inzulínom glargínom spolu s orálnymi antidiabetikami alebo bez nich. Interná Med 2013; 13(9): 411–417.

34. Martinka E, Mišániková M. Včasná liečba inzulínom u pacientov s diabetes mellitus 2. typu a jej princípy.

35. Martinka E, Uličiansky V, Mokáň M et al. Konsenzuálny terapeutický algoritmus pre diabetes mellitus 2. typu. Forum Diab 2016; 5(2): 111–120.

36. Martinka E. Inzulín v terapeutickej schéme diabetes mellitus 2. typu. Forum Diab 2017; 6(2): 69–77.

37. Mathieu C, Rodbard HW, Cariou B et al. A comnparison of adding liraglutide versusu a single daily dose of insulin aspart to insulin degludec in subjects with type 2 diabetes (BRGIN: Victoza Add-On). Diabetes Obes Metab 2014; 16(7): 636–644. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.12262>.

38. Mišániková M, Martinka E. Inzulín glargín 300 U/ml v reálnej klinickej praxi. Diabetes a obezita 17(34); 2017: 35–46.

39. Marso SP, Daniels GH, Brown-Frandsen K et al. [LEADER Steering Committee. LEADER Trial Investigators]. 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>.

40. Marso SP, Bain SC, Consoli Aet al. [SUSTAIN-6 Investigators]. 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>.

41. Mechanick JI, Marchetti AE, Apovian C et al. Diabetes-specific nutrition algorithm: a transcultural program to optimize diabetes and prediabetes care. Curr Diab Rep 2012; 12(2): 180–194. Dostupné z DOI: <http://dx.doi.org/10.1007/s11892–012–0253-z>.

42. Mokan M, Mitrakou A, Veneman T et al. Hypoglycemia unawareness in IDDM. Diabetes Care 1994; 17(12): 1397–403.

43. Nishikawa T, Araki E. Involvement of advanced glycation end-products in ‘hyperglycemic memory. J Diabetes Investig 2016; 7(3): 297–299. Dostupné z DOI: <http://dx.doi.org/10.1111/jdi.12405>.

44. Neal B, Perkovic V, Mahaffey KWet al. [CANVAS Program Collaborative Group]. Canagliflozin 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>.

45. MZSR. Aktuálne znenie indikačných obmedzení pre preskripciu liekov hradených z verejného poistenia. Dostupné z WWW: <http://www.health.gov.sk/Clanok?lieky201605>.

46. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007; 356(24): 2457–2471. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa072761>. Erratum in N Engl J Med 2007; 357(1): 100.

47. Pfeffer MA, Claggett B, Diaz R et al. 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>.

48. Gerstein HC, Bosch J, Dagenais GR et al. [The Origin Trial Investigators. Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia. N Engl J Med 2012; 367(4): 319–328. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1203858>.

49. [ORIGIN Trial Investigators]. Cardiovascular and other outcomes postintervention with insulin glargine and omega-3 fatty acids (ORIGINALE). Diabetes Care 2016; 39(5): 709–716. Dostupné z DOI: <http://dx.doi.org/10.2337/dc15–1676>.

50. Read PA, Khan FZ, Heck PM et al. DPP-4 inhibition by sitagliptin improves the myocardial response to dobutamine stress and mitigates stunning in a pilot study of patients with coronary artery disease. Circ Cardiovasc Imaging 2010; 3(2): 195–201. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCIMAGING.109.899377>.

51. Rosenstock J, Aronson R, Grunberger G et al. Benefits of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide, Versus Insulin Glargine and Lixisenatide Monocomponents in Type 2 Diabetes Inadequately Controlled on Oral Agents: The LixiLan-O Randomized Trial. Diabetes Care 2016; 39(11): 2026–2035. Dostupné z DOI: <https://doi.org/10.2337/dc16–0917>. Erratum in Erratum. Benefits of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide, Versus Insulin Glargine and Lixisenatide Monocomponents in Type 2 Diabetes Inadequately Controlled on Oral Agents: The LixiLan-O Randomized Trial. Diabetes Care 2016; 39:2026–2035. [Diabetes Care 2017]

52. Rosenstock J, Ferrannini E. Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, and Preventable Safety Concern With SGLT2 Inhibitors. Diabetes Care 2015; 38(9): 1638–1642. Dostupné z DOI: <http://dx.doi.org/10.2337/dc15–1380>.

53. Rosenstock J, Marx N, Neubacher D et al. Cardiovascular safety of linagliptin in type 2 diabetes: a comprehensive patient-level pooled analysis of prospectively adjudicated cardiovascular events. Cardiovasc Diabetol 2015; 14: 57. Dostupné z DOI: <http://dx.doi.org/10.1186/s12933–015–0215–2>.

54. Roumie CL, Min JY, D’Agostino McGowan L et al. Griffin Comparative Safety of Sulfonylurea and Metformin Monotherapy on the Risk of Heart Failure: A Cohort Study. J Am Heart Assoc 2017; 6(4). pii: e005379. Dostupné z DOI: <http://dx.doi.org/10.1161/JAHA.116.005379>.

55. Sarwar N, Gao P, Seshasai SR et al. [Emerging Risk Factors Collaboration]. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 2010; 375(9733): 2215–2222. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(10)60484–9>. Erratum in Lancet 2010; 376(9745): 958. Hillage HL.

56. Sattar N, McLaren J, Kristensen SL et al. SGLT2 Inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms? Diabetologia 2016; 59(7): 1333–1339. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–016–3956-x>. Erratum in Erratum to: SGLT2 Inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms? [Diabetologia 2016].

57. Scirica BM, Bhatt DL, Braunwald E et al. [SAVOR-TIMI 53 Steering Committee and Investigators]. Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus N Engl J Med 2013; 369(14): 1317–1326. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1307684>.

58. Scott GN. Early Intensive Insulin in Type 2 Diabetes. Medscape -– Jan 12, 2017. Dostupné z WWW: <https://www.medscape.com/viewarticle/874182>.

59. Shah AD, Langenberg C, Rapsomaniki E et al. Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1·9 million people. Lancet Diabetes Endocrinol 2015; 3(2): 105–113. Dostupné z DOI: <http://dx.doi.org/10.1016/S2213–8587(14)70219–0>.

60. Schernthaner G, Currie CJ, Schernthaner GH.. Do we still need pioglitazone for the treatment of type 2 diabetes? A risk-benefit critique in 2013. Diabets Care 2013; 36(Suppl 2): S155-S161. Dostupné z DOI: <http://dx.doi.org/10.2337/dcS13–2031>.

61. 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>.

62. Schramm TK, Gislason GH, Vaag A et al. Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study. Eur Heart J 2011; 32(15): 1900–1908. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehr077>. Erratum in Eur Heart J 2012; 33(10): 1183.

63. Tkáč 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>.

64. Uliciansky V. Liečba diabtes mellitus 2. typu. In: Mokáň M, Martinka E, Galajda P. Diabetes mellitus a vybrané metabolické ochorenia. Vydavateľstvo P+M: Turany 2008: 276–322. ISBN 978–80–969713–9-8.

65. [UK Prospective Diabetes Study (UKPDS) Group]. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352(9131): 837–853. Erratum in Lancet 1999; 354(9178): 602.

66. [UK Prospective Diabetes Study Group (UKPDS)]. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352(9131): 854–865. Erratum in Lancet 1998; 352(9139): 1558.

67. 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>.

68. Weng J1, Li Y, Xu W et al. Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial. Lancet 2008; 371(9626): 1753–1760. Dostupné z DOI: <http://dx.doi.org/10.1016/ S0140–6736(08)60762-X>.

69. Ye F, Rishi A, Kaur A, et al. Real-world assessment of patient characteristics and clinical outcomes of early users of the new insulin glargine 300 U/mL. Diabetes 2016; 65(Suppl 1):A243.

70. Yki-Järvinen H, Bergenstal R, Ziemen M et al. [EDITION 2 Study Investigators]. New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using oral agents and basal insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 2). Diabetes Care 2014; 37(12): 3235–3243. Dostupné z DOI: <http://dx.doi.org/10.2337/dc14–0990>.

71. 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>.

72. Zoungas S, Chalmers J, Neal B et al. Follow-up of Blood-Pressure Lowering and Glucose Control in Type 2 Diabetes. N Engl J Med 2014; 371(15): 1392–1406. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1407963>.

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