Neue Antidiabetika

Zusammenfassung

Diabetes steigert das Risiko für Herz-Kreislauf-Erkrankungen und hat eine zunehmende Prävalenz. Die Therapie des Diabetes stellte bisher ein Dilemma dar, da viele Therapien zwar den Blutzucker, aber nicht kardiovaskuläre Ereignisse reduzierten. Erst Glukagon-like Peptid-1-Rezeptor-Agonisten (GLP1) und Natrium/Glukose-Cotransporter-2(SGLT2)-Inhibitoren senkten deutlich kardiovaskuläre Endpunkte, und SGLT2-Inhibitoren beugten darüber hinaus der Entwicklung einer Herzinsuffizienz vor. Die Glukosesenkung an sich ist daher nicht entscheidend für den Schutz vor Herz-Kreislauf-Erkrankungen. Die neuen Leitlinien der Europäischen Gesellschaft für Kardiologie stellen daher bei Patienten mit Diabetes und hohem kardiovaskulären Risiko die Verwendung von GLP1-Rezeptor-Agonisten und SGLT2-Inhibitoren der Behandlung mit Metformin voran. Die neuen Studiendaten eröffnen zudem neue metabolische Ansatzpunkte für die Behandlung von Herz-Kreislauf-Erkrankungen auch unabhängig vom Vorliegen eines Diabetes.

Abstract

Diabetes increases the risk for cardiovascular diseases and rises in prevalence. The treatment of diabetes has so far been a therapeutic dilemma, since most treatments reduced blood glucose, but not cardiovascular events. In recent trials, glucagon-like peptide 1 (GLP1) receptor agonists or sodium/glucose-cotransporter 2 (SGLT2) inhibitors reduced cardiovascular endpoints, and SGLT2-inhibitors also prevented the development of heart failure. Therefore, lowering blood glucose per se is not sufficient to optimize cardiovascular risk. The recent Guidelines of the European Society of Cardiology suggest to treat patients with diabetes and a high cardiovascular risk with either GLP1-receptor agonists or SGLT2-inhibitors before the initiation of metformin, which remains treatment of first choice for patients at low or moderate cardiovascular risk. Furthermore, metabolic treatments may improve the prognosis of cardiovascular patients independent of the presence of diabetes.

Was ist wichtig?

• GLP1-Rezeptor-Agonisten und SGLT2-Inhibitoren sind die einzigen Antidiabetika, die kardiovaskuläre Endpunkte reduzieren.

• SGLT2-Inhibitoren beugen zusätzlich der Entwicklung einer Herzinsuffizienz vor.

• SGLT2-Inhibitoren verbessern die Prognose bei Herzinsuffizienz auch unabhängig vom Vorliegen eines Diabetes.

• In den neuen Europäischen Leitlinien werden daher GLP1-Rezeptor-Agonisten und SGLT2-Inhibitoren der Therapie mit Metformin bei Patienten mit Diabetes und hohem Risiko vorangestellt.

Schlüsselwörter

Diabetes mellitus Typ 2 - kardiovaskuläres Risiko - Herzinsuffizienz - SGLT2-Inhibitoren - GLP1-Rezeptor-Agonisten

Key words

cardiovascular risk - SGLT2-inhibitors - GLP1-receptor agonists - heart failure - type 2 diabetes

Publication History

Article published online:
14 August 2020

• Literatur

• 1 Bilano V, Gilmour S, Moffiet T. et al. Global trends and projections for tobacco use, 1990–2025: an analysis of smoking indicators from the WHO Comprehensive Information Systems for Tobacco Control. Lancet 2015; 385: 966-976
• 2 NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet 2016; 387: 1513-1530
• 3 Gilbert RE, Krum H. Heart failure in diabetes: effects of anti-hyperglycaemic drug therapy. Lancet 2015; 385: 2107-2117
• 4 Nichols GA, Hillier TA, Erbey JR. et al. Congestive Heart Failure in Type 2 Diabetes. Prevalence, incidence, and risk factors. Diabetes Care 2001; 24: 1614-1619
• 5 Udell JA, Cavender MA, Bhatt DL. et al. Glucose-lowering drugs or strategies and cardiovascular outcomes in patients with or at risk for type 2 diabetes: a meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol 2015; 3: 356-366
• 6 Cosmi F, Shen L, Magnoli M. et al. Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes. Eur J Heart Fail 2018; 20: 888-895
• 7 Shen L, Rørth R, Cosmi D. et al. Insulin treatment and clinical outcomes in patients with diabetes and heart failure with preserved ejection fraction. Eur J Heart Fail 2019; 21: 974-984
• 8 Lehrke M, Marx N. New antidiabetic therapies: innovative strategies for an old problem. Curr Opin Lipidol 2012; 23: 569-575
• 9 Kahles F, Meyer C, Mollmann J. et al. GLP-1 secretion is increased by inflammatory stimuli in an IL-6-dependent manner, leading to hyperinsulinemia and blood glucose lowering. Diabetes 2014; 63: 3221-3229
• 10 Cummings DE, Overduin J. Gastrointestinal regulation of food intake. J Clin Invest 2007; 117: 13-23
• 11 Rosenstock J, Kahn SE, Johansen OE. et al. Effect of Linagliptin vs. Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial. JAMA 2019; 322: 1155-1166
• 12 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: 69-79
• 13 Scheen AJ. Cardiovascular Effects of New Oral Glucose-Lowering Agents: DPP-4 and SGLT-2 Inhibitors. Circ Res 2018; 122: 1439-1459
• 14 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
• 15 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
• 16 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: 121-130
• 17 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: 131-138
• 18 Husain M, Birkenfeld AL, Donsmark M. et al. Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2019; 381: 841-851
• 19 Heerspink HJ, Perkins BA, Fitchett DH. et al. Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus: Cardiovascular and Kidney Effects, Potential Mechanisms, and Clinical Applications. Circulation 2016; 134: 752-772
• 20 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
• 21 Wiviott SD, Raz I, Bonaca MP. et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2018; 380: 347-357
• 22 Neal B, Perkovic V, Mahaffey KW. et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med 2017; 377: 644-657
• 23 Wanner C, Inzucchi SE, Zinman B. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med 2016; 375: 1801-1802
• 24 Cannon CP, McGuire DK, Pratley R. et al. Design and baseline characteristics of the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes trial (VERTIS-CV). Am Heart J 2018; 206: 11-23
• 25 Zelniker TA, Wiviott SD, Raz I. et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet 2019; 393: 31-39
• 26 Kato ET, Silverman MG, Mosenzon O. et al. Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus. Circulation 2019; 139: 2528-2536
• 27 McMurray JJV, Solomon SD, Inzucchi SE. et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med 2019; 381: 1995-2008
• 28 Lopaschuk GD, Verma S. Empagliflozinʼs Fuel Hypothesis: Not so Soon. Cell Metab 2016; 24: 200-202
• 29 Ho KL, Karwi QG, Wagg C. et al. Ketones can become the major fuel source for the heart but do not increase cardiac efficiency. Cardiovasc Res 2020;
• 30 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: 722-726
• 31 Bertero E, Prates Roma L, Ameri P. et al. Cardiac effects of SGLT2 inhibitors: the sodium hypothesis. Cardiovasc Res 2018; 114: 12-18
• 32 Maack C, Lehrke M, Backs J. et al. Heart failure and diabetes: metabolic alterations and therapeutic interventions: a state-of-the-art review from the Translational Research Committee of the Heart Failure Association-European Society of Cardiology. Eur Heart J 2018; 39: 4243-4254
• 33 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: 255-323
• 34 Marx N, Frantz S, Gitt AK. et al. Kommentar zu den Leitlinien (2019) der European Society of Cardiology (ESC) zu „Diabetes, Prädiabetes und kardiovaskuläre Erkrankungen“. Kardiologe 2020; 14: 162-167