Klinischer Nutzen der inkretinbasierten Therapien – Verbesserte Behandlung bei Typ–2–Diabetes

Die Therapie des Typ–2–Diabetes ist nach wie vor schwierig. Therapeutische Ziele werden häufig nicht erreicht, und die Erkrankung einschließlich der mikro– und makrovaskulären Folgeerscheinungen schreitet fort. Inkretinbasierte Therapien haben neben der Wirkung auf die Glukosehomöostase und Besserung der Funktion der pankreatischen Betazellen weitere Effekte wie Senkung von Körpergewicht und Blutdruck, die die Situation und Lebensqualität des Patienten mit Typ–2–Diabetes langfristig möglicherweise günstig beeinflussen können.

Therapy of diabetes mellitus type 2 is still difficult. The therapeutic goals are often not reached, the disease with micro– and macrovascular sequelaes is progressing. Inkretin–based therapies have besides the effects on glucose homeostasis further and amelioration of the pancreatic beta cell function further beneficial effects on body weight and blood pressure. These effects can possibly improve the situation and quality of life of a patient with type 2 diabetes.

Diabetes mellitus type 2 - cardiovascular risk - Inkretinmimetics - DPP–4–inhibitors - Exenatide - Liraglutide - Sitagliptin - Vildagliptin

Literatur

• 1 Scherbaum W, Haak T.. Medikamentöse antihyperglykämische Therapie des Diabetes mellitus Typ 2. Update der Evidenz–basierten Leitlinie der Deutschen Diabetes–Gesellschaft; 2008. Oktober 2008.  www.deutsche-diabetes-gesellschaft.de
• 2 Pitocco D, Valle D, Rossi A, Gentilella R.. Unmet needs among patients with type 2 diabetes and secondary failure to oral anti–diabetic agents.  J Endocrinol Invest. 2008;  31 371-379
• 3 Nauck M, Stöckmann F. et al. . Reduced incretin eff ect in type 2 (non–insulin–dependent) diabetes.  Diabetologia. 1986;  29 46-52
• 4 Chia CW, Egan JM.. Incretin–based therapies in type 2 diabetes mellitus.  J Clin Endocrinol Metab. 2008;  93 3703-3716
• 5 Meier JJ, Schmidt WE, Klein HH.. New concepts in the treatment of type 2 diabetes.  Internist. 2007;  48 700-707
• 6 Madsbad S.. Liraglutide eff ect and action in diabetes (LEAD) trial.  Expert Rev Endocrinol Metab. 2009;  4 119-129
• 7 Marre M, Shaw J. et al. .Liraglutide, a once–dailyhuman GLP–1 analog, added to a sulfonylurea off ers signifi – cantly better glycemic control and favorable weight change compared with rosiglitazone and SU combination therapy in subjects with type 2 diabetes. ADA, 68th Scientifi c Sessions:13–0R
• 8 Nauck M, Frid A. et al. . Effi cacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide eff ect and action in diabetes)–2 study.  Diabetes Care. 2009;  32 84-90
• 9 Garber A, Henry R. et al. . Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD–3 Mono): a randomised, 52–week, phase III, doubleblind, parallel–treatment trial.  Lancet. 2009;  373 473-481
• 10 Zinman B, Gerich J, Buse JB. et al. .Effi cacy and safety of the human GLP–1–analog liraglutide in combination with metformin and TZD in patients with type 2 diabetes mellitus (LEAD–4 Met+TZD). Diabetes Care 2009: 08-2124
• 11 Russell–Jones D, Vaag A. et al. . Signifi cantly better glycemic control and weight reduction with liraglutide, a once–daily human GLP–1 analog, compared with insulin glargine: all as add–on to metformin and a sulfonylurea in type–2 diabetes.  Diabetes. 2008;  57
• 12 Blonde L, Rosenstock J. et al. .Liraglutide: superior glycemic control vs exenatide when added to metformin and/ode SU in type 2 diabetes. Canadian Diabetes Association Annual General Meeting, Montreal, 16. Oktober 2008
• 13 Jendle J, Emamaullee JA.. Liraglutide, a once–daily human GLP–1 analog, reduces fat percentage, visceral and subcutaneous adipose tissue and hepatic steatosis compared with glimepiride when added to metformin in subjects with type 2 diabetes. ADA, 68th Scientifi c Sessions 2008
• 14 Colagiuri S, Frid A. et al. .The once–daily human GLP–1 analog liraglutide reduces systolic blood pressure in patients with type 2 diabetes. ADA, 68th Scientifi c Sessions
• 15 UK Prospective Diabetes Study (UKPDS) Group. . U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group.  Diabetes. 1995;  44 1249-1258
• 16 Amori RE, Lau J. et al. . Effi cacy and safety of incretin therapy in type 2 diabetes. Systematic review and meta–analysis.  JAMA. 2007;  298 194-206
• 17 Fischer S, Bornstein SR.. Neue orale Antidiabetika. Klinische Perspektiven.  Internist. 2008;  49 495-501
• 18 Nauck MA.  Inkretinmimetika und Inkretinverstärker. Neue Diabetesmedikamente auf der Basis physiologischer insulinsekretionssteigernder Darmhormone.  Diabetologe. 2007;  3 387-398
• 19 Mistry GC, Maes AL, Lasseter KC. et al. . Eff ect of sita glitpin, a dipeptidyl–peptidase–4 inhibitor, on blood pressure in nondiabetic patients mit mild to moderate hypertension.  J Clin Pharmacol. 2008;  48 592-598
• 20 Raz I, Hanefeld M, Xu L. et al. . Effi cacy and safety of the dipeptidyl peptidase IV inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus.  Dia betologia. 2006;  49 2564-2571
• 21 Skyler JS, Bergenstal R. et al. . Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA diabetes trials: a position statement of the American Diabetes Association and a scientifi c statement of the American College of Cardiology Foundation and the American Heart Association.  Diabetes Care. 2009;  32 187-192
• 22 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 (UKPDS33).  Lancet. 1998;  352 837-853
• 23 Holman RR, Paul SK. et al. . 10–year follow–up of intensive glucose control in type 2 diabetes.  N Engl J Med. 2008;  359 1577-1589
• 24 Drucker DJ, Nauck MA.. The incretin system: glucagon–like peptide–1 receptor agonists and dipeptidyl peptidase–4 inhibitors in type 2 diabetes.  Lancet. 2006;  368 1696-1705
• 25 Fachinformation. Byetta. Fachinformation 2009; (März 2009). 
• 26 Gallwitz B.. Liraglutide.  Drugs of the Future. 2008;  33 13-20
• 27 Klonoff DC, Buse JB, Nielsen LL. et al. . Exenatide eff ects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years.  Curr Med Res Opin. 2008;  24 275-286

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