Subscribe to RSS
DOI: 10.1055/s-0042-121159
Neue Antidiabetika und kardiovaskuläre Outcome-Studien
Novel antidiabetic medications and cardiovascular outcome studiesPublication History
Publication Date:
01 September 2017 (online)
![](https://www.thieme-connect.de/media/ds/201704/lookinside/thumbnails/dus-2459529_10-1055-s-0042-121159-1.jpg)
Abstract
Type 2 diabetes mellitus (T2DM) represents a major risk factor for the development of cardiovascular events, and cardiovascular mortality determines overall mortality in these patients. So far, glucose lowering per se has demonstrated a small effect in reduction of cardiovascular risk in T2DM patients. Due to regulatory purposes, since 2008 all novel antidiabetic medications, such as DPP4 inhibitors, GLP-1 receptor agonists and SGLT2 inhibitors are investigated in dedicated cardiovascular outcome trials to demonstrate cardiovascular safety (non-inferiority trials). While the currently completed cardiovascular outcome trials for the DPP4 inhibitors sitagliptin, saxagliptin and alogliptin consistently demonstrated a neutral effect on cardiovascular risk, those trials for the GLP-1 receptor agonists revealed differential outcomes. Lixisenatide effects were neutral on cardiovascular outcomes while Liraglutide and Semaglutide demonstrated a reduction in cardiovascular risk. Most impressively was cardiovascular mortality, overall mortality and hospitalisation for heart failure reduced by the SGLT2 inhibitor empagliflozin in its dedicated outcome trial. These results strongly imply that certain novel antihyperglycaemic agents bear the potential to strongly reduce cardiovascular risk in patients with T2DM beyond their glucose lowering potency. The potential to reduce cardiovascular risk in patients with T2DM will selectively determine the clinical application of antidiabetic medications in the future.
Diabetes mellitus Typ 2 ist anerkanntermaßen einer der Hauptrisikofaktoren für die Entwicklung kardiovaskulärer Erkrankungen. Aufgrund der Vorgaben der Zulassungsbehörden werden neue Antidiabetika in kardiovaskulären Endpunktstudien untersucht. Derzeit sind dies Medikamente aus der Gruppe der DPP4-Inhibitoren, GLP-1-Rezeptoragonisten und SGLT2-Inhibitoren. Die Ergebnisse der derzeit vorliegenden kardiovaskulären Outcome-Studien werden im Folgenden dargestellt und diskutiert.
-
Literatur
- 1 Seshasai SR, Kaptoge S. Emerging Risk Factors C. et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med 2011; 364: 829-841
- 2 Campos C. Chronic hyperglycemia and glucose toxicity: pathology and clinical sequelae. Postgrad Med 2012; 124: 90-97
- 3 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: 837-853
- 4 UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854-865
- 5 Gerstein HC, Miller ME. Group AS. et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med 2011; 364: 818-828
- 6 Patel A, MacMahon S. Group AC. et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008; 358: 2560-2572
- 7 Hayward RA, Reaven PD, Wiitala WL. et al. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015; 372: 2197-2206
- 8 Dormandy JA, Charbonnel B, Eckland DJ. et al. 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 2005; 366: 1279-1289
- 9 Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007; 356: 2457-2471
- 10 Home PD, Pocock SJ, Beck-Nielsen H. et al. Rosiglitazone evaluated for cardiovascular outcomes-an interim analysis. N Engl J Med 2007; 357: 28-38
- 11 Bethel MA, Sourij H. Impact of FDA guidance for developing diabetes drugs on trial design: from policy to practice. Curr Cardiol Rep 2012; 14: 59-69
- 12 Baigent C, Keech A, Kearney PM. et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005; 366: 1267-1278
- 13 Ussher JR, Drucker DJ. Cardiovascular actions of incretinbased therapies. Circ Res 2014; 114: 1788-1803
- 14 Seufert J, Gallwitz B. The extra-pancreatic effects of GLP-1 receptor agonists: a focus on the cardiovascular, gastrointestinal and central nervous systems. Diabetes Obes Metab 2014; 16: 673-688
- 15 Ampudia-Blasco FJ, Benhamou PY, Charpentier G. et al. A decision support tool for appropriate glucose-lowering therapy in patients with type 2 diabetes. Diabetes Technol Ther 2015; 17: 194-202
- 16 White WB, Cannon CP, Heller SR. et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013; 369: 1327-1335
- 17 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: 1317-1326
- 18 Green JB, Bethel MA, Armstrong PW. et al. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2015; 373: 232-242
- 19 Scirica BM, Braunwald E, Raz I. et al. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation 2014; 130: 1579-1588
- 20 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: 2247-2257
- 21 Marso SP, Daniels GH, Brown-Frandsen K. et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016; 375: 311-322
- 22 Marso SP, Bain SC, Consoli A. et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2016 375. 1834-1844
- 23 Novo Nordisk Worldwide. Semaglutide significantly reduces the risk of major adverse cardiovascular events in the SUSTAIN 6 trial. Im Internet: http://www.novonordisk.com/media/news-details.2007805.html Stand: 6.5.2016
- 24 Novo Nordisk Worldwide. Victoza significantly reduces the risk of major adverse cardiovascular events in the LEADER trial. Im Internet: https://www.novonordisk.com/bin/getPDF.1991879.pdf Stand: 6.5.2016
- 25 Seufert J. SGLT2 inhibitors – an insulin-independent therapeutic approach for treatment of type 2 diabetes: focus on canagliflozin. Diabetes Metab Syndr Obes 2015; 8: 543-554
- 26 Seufert J. SGLT-2-Inhibition mit Canagliflozin: Eine neue Option in der Therapie des Typ-2-Diabetes. Dtsch Med Wochenschr 2014; 139: 1-8
- 27 Zinman B, Wanner C, Lachin JM. et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 2015; 373: 2117-2128