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Kardiovaskuläre Aspekte der Diabetestherapie

Endlich Grund zur Freude für Kardiologen

Cardiovascular aspects of diabetes treatment

Finally a reason for cardiologists to be pleased

  • Arzneimitteltherapie
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Zusammenfassung

Bei Patienten mit einem Diabetes mellitus Typ 2 bestimmen kardiovaskuläre Komplikationen maßgeblich die Morbidität und Mortalität. In der Vergangenheit haben große klinische Studien zum Einfluss einer blutzuckersenkenden Therapie auf kardiovaskuläre Erkrankungen ein widersprüchliches Bild ergeben. Im Jahr 2008 haben die Zulassungsbehörden die Vorgaben für den Beleg der kardiovaskulären Sicherheit neuer antidiabetischer Substanzen geändert. Seitdem wurden zahlreiche kardiovaskuläre Endpunktstudien zum Beleg der Sicherheit neuer Substanzen initiiert. Erste Daten aus diesen Sicherheitsstudien liegen jetzt vor; die Ergebnisse sind vielversprechend. Während für die Behandlung mit Dipeptidylpeptidase-4(DPP-4)-Hemmern und dem kurz wirksamen Glucagon-like-peptide-1(GLP-1)-Rezeptor-Agonisten Lixisenatid die kardiovaskuläre Sicherheit belegt werden konnte, wurden für den Sodium-glucose-transporter-2(SGLT-2)-Hemmer Empagliflozin und den lang wirksamen GLP-1-Rezeptor-Agonisten Liraglutid sogar signifikante kardiovaskuläre Vorteile gezeigt. Die kardiovaskulären Vorteile dieser Substanzen werden neue Therapiestrategien zur Behandlung des Diabetes mellitus Typ 2 nach sich ziehen.

Abstract

Cardiovascular disease significantly determines morbidity and mortality in patients with diabetes mellitus type 2. Large clinical trials in the past left controversial evidence about the effect of blood glucose-lowering treatments on cardiovascular outcomes. In 2008, the regulatory authorities defined new requirements on cardiovascular safety data for the approval of new drugs for the treatment of type 2 diabetes mellitus. Since then, numerous large safety studies have been initiated to prove cardiovascular noninferiority of new antidiabetic drugs. Preliminary data from these safety studies have become available and provided promising results. While treatment with DPP-4 inhibitors and the short acting GLP-1 receptor agonist lixisenatide were shown to be safe, treatment with the SGLT-2 inhibitor empagliflozin and the long-acting GLP-1 receptor agonist liraglutide even significantly improved cardiovascular outcomes in patients with type 2 diabetes mellitus. With the evidence of cardiovascular benefits of the new drugs, new treatment strategies for patients with diabetes mellitus type 2 are expected.

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Literatur

  1. Bianchi C, Miccoli R, Del PS (2013) Hyperglycemia and vascular metabolic memory: truth or fiction? Curr Diab Rep 13:403–410

    Article  CAS  PubMed  Google Scholar 

  2. Committee for Medicinal Products for Human Use (CHMP) (2010) Guideline on clinical investigation of medicinal products in the treatment of diabetes mellitus

    Google Scholar 

  3. Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, Skene AM, Tan MH, Lefebvre PJ, Murray GD, Standl E, Wilcox RG, Wilhelmsen L, Betteridge J, Birkeland K, Golay A, Heine RJ, Koranyi L, Laakso M, Mokan M, Norkus A, Pirags V, Podar T, Scheen A, Scherbaum W, Schernthaner G, Schmitz O, Skrha J, Smith U, Taton J (2005) Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 366:1279–1289

    Article  CAS  PubMed  Google Scholar 

  4. Drucker DJ (2016) The cardiovascular biology of glucagon-like peptide-1. Cell Metab 24:15–30

    Article  CAS  PubMed  Google Scholar 

  5. Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, Zieve FJ, Marks J, Davis SN, Hayward R, Warren SR, Goldman S, McCarren M, Vitek ME, Henderson WG, Huang GD (2009) Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 360:129–139

    Article  CAS  PubMed  Google Scholar 

  6. Ferrannini E, Mark M, Mayoux E (2016) CV protection in the EMPA-REG OUTCOME trial: a „thrifty substrate“ hypothesis. Diabetes Care 39:1108–1114

    Article  PubMed  Google Scholar 

  7. Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O (2003) Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 348:383–393

  8. Gaede P, Oellgaard J, Carstensen B, Rossing P, Lund-Andersen H, Parving HH, Pedersen O (2016) Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial. Int J Obes Relat Metab Disord 59:2298–2307

    CAS  Google Scholar 

  9. Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O (2003) Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 348:383–393

    Article  PubMed  Google Scholar 

  10. Gerstein HC, Miller ME, Genuth S, Ismail-Beigi F, Buse JB, Goff DC, Jr., Probstfield JL, Cushman WC, Ginsberg HN, Bigger JT, Grimm RH, Jr., Byington RP, Rosenberg YD, Friedewald WT (2011) Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med 364:818–828

  11. Gerstein HC, Bosch J, Dagenais GR, Diaz R, Jung H, Maggioni AP, Pogue J, Probstfield J, Ramachandran A, Riddle MC, Ryden LE, Yusuf S (2012) Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 367:319–328

    Article  CAS  PubMed  Google Scholar 

  12. Gerstein HC, Miller ME, Byington RP, Goff DC Jr., Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr., Probstfield JL, Simons-Morton DG, Friedewald WT (2008) Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 358:2545–2559

    Article  CAS  PubMed  Google Scholar 

  13. Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, Josse R, Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Pencina MJ, Standl E, Stein PP, Suryawanshi S, Van de Werf F, Peterson ED, Holman RR (2015) Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 373:232–242

    Article  CAS  PubMed  Google Scholar 

  14. Heerspink HJ, Perkins BA, Fitchett DH, Husain M, Cherney DZ (2016) Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation 134:752–772

    Article  CAS  PubMed  Google Scholar 

  15. Hirshberg B, Raz I (2011) Impact of the U.S. Food and Drug Administration cardiovascular assessment requirements on the development of novel antidiabetes drugs. Diabetes Care 34(Suppl 2):S101–S106

    Article  PubMed  PubMed Central  Google Scholar 

  16. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA (2008) 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 259:1577–1589

    Article  Google Scholar 

  17. Holman RR, Sourij H, Califf RM (2014) Cardiovascular outcome trials of glucose-lowering drugs or strategies in type 2 diabetes. Lancet 383:2008–2017

  18. Home PD, Pocock SJ, Beck-Nielsen H, Curtis PS, Gomis R, Hanefeld M, Jones NP, Komajda M, McMurray JJ (2009) Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet 373:2125–2135

    Article  CAS  PubMed  Google Scholar 

  19. Inzucchi SE, Zinman B, Wanner C, Ferrari R, Fitchett D, Hantel S, Espadero RM, Woerle HJ, Broedl UC, Johansen OE (2015) SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of ongoing outcome trials. Diab Vasc Dis Res 12:90–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsboll T (2016) Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 375:1834–1844

    Article  CAS  PubMed  Google Scholar 

  21. Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB (2016) Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 375(4):311–322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsboll T (2016) Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 375:1834–1844

  23. Neal B, Perkovic V, de ZD, Mahaffey KW, Fulcher G, Stein P, Desai M, Shaw W, Jiang J, Vercruysse F, Meininger G, Matthews D (2013) Rationale, design, and baseline characteristics of the Canagliflozin Cardiovascular Assessment Study (CANVAS) – a randomized placebo-controlled trial. Am Heart J 166:217–223

  24. Nissen SE, Wolski K (2007) Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 356:2457–2471

    Article  CAS  PubMed  Google Scholar 

  25. Nissen SE, Wolski K (2010) Rosiglitazone revisited: an updated meta-analysis of risk for myocardial infarction and cardiovascular mortality. Arch Intern Med 170:1191–1201

    Article  CAS  PubMed  Google Scholar 

  26. Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Liu L, Mancia G, Mogensen CE, Pan C, Poulter N, Rodgers A, Williams B, Bompoint S, de Galan BE, Joshi R, Travert F (2008) Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 358:2560–2572

    Article  CAS  PubMed  Google Scholar 

  27. Pfeffer MA, Claggett B, Diaz R, Dickstein K, Gerstein HC, Kober LV, Lawson FC, Ping L, Wei X, Lewis EF, Maggioni AP, McMurray JJ, Probstfield JL, Riddle MC, Solomon SD, Tardif JC (2015) Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med 373:2247–2257

    Article  CAS  PubMed  Google Scholar 

  28. Rosenstock J, Marx N, Kahn SE, Zinman B, Kastelein JJ, Lachin JM, Bluhmki E, Patel S, Johansen OE, Woerle HJ (2013) Cardiovascular outcome trials in type 2 diabetes and the sulphonylurea controversy: rationale for the active-comparator CAROLINA trial. Diab Vasc Dis Res 10:289–301

  29. Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I (2013) Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 369:1317–1326

    Article  CAS  PubMed  Google Scholar 

  30. U.S.Department of Health and Human Services Food and Drug Administration (2016) Guidance for industry diabetes mellitus – evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). December 2008

  31. UK Prospective Diabetes Study (UKPDS) Group (1998) 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 352:837–853

    Article  Google Scholar 

  32. Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von EM, Mattheus M, Johansen OE, Woerle HJ, Broedl UC, Zinman B (2016) Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 375(4):323–334

    Article  CAS  PubMed  Google Scholar 

  33. White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris GL, Perez AT, Fleck PR, Mehta CR, Kupfer S, Wilson C, Cushman WC, Zannad F (2013) Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 369:1327–1335

    Article  CAS  PubMed  Google Scholar 

  34. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE (2015) Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373:2117–2128

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Profil Institut für Stoffwechselforschung, Neuss, Deutschland

    T. Forst

  2. Universitätsmedizin, I. Medizinische Klinik, Schwerpunkt Endokrinologie und Stoffwechselerkrankungen, Johannes Gutenberg-Universität Mainz, Mainz, Deutschland

    T. Forst & M. M. Weber

  3. Profil Mainz GmbH & Co. KG, Rheinstr. 4C, 55116, Mainz, Deutschland

    T. Forst & L. Plum-Mörschel

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Correspondence to T. Forst.

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Interessenkonflikt

T. Forst ist als Berater für AstraZeneca, Ely Lilly, BMS, Sanofi und Boehringer Ingelheim tätig. Er hat Vortragshonorare von AstraZeneca, Eli Lilly, Novo Nordisk, Sanofi, BMS, Berlin Chemie, Novartis und Boehringer Ingelheim erhalten. M.M. Weber ist als Berater für Novo Nordisk, Eli Lilly und Boehringer Ingelheim tätig und hat Vortragshonorare von Boehringer Ingelheim und MSD Sharp & Dohme GmbH erhalten. L. Plum-Mörschel gibt an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Forst, T., Plum-Mörschel, L. & Weber, M.M. Kardiovaskuläre Aspekte der Diabetestherapie. Internist 58, 293–302 (2017). https://doi.org/10.1007/s00108-017-0189-0

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