Zusammenfassung
Das Inkretin „Glukagon-like peptide-1” (GLP-1) wird in den endokrinen L-Zellen des
Darms gebildet und stimuliert Glukose-abhängig die Synthese und Sekretion von Insulin.
Der Stoffwechsel des Typ-2-Diabetikers kann durch die zusätzliche Gabe von GLP-1 wesentlich
verbessert werden, jedoch wird dieses Peptid innerhalb von Minuten enzymatisch abgebaut.
Der synthetische GLP-1-Agonist Exenatid unterliegt nicht diesem Metabolismus und wurde
kürzlich als erste Substanz dieser Klasse in den USA zur adjuvanten Behandlung von
Typ-2-Diabetikern zugelassen, bei denen keine ausreichende Blutzucker-Kontrolle mit
Metformin und/oder Sulfonylharnstoffen erreicht werden kann. Erste klinische Studien
zeigen, dass in der adjuvanten Therapie die Blutzuckersenkung unter zweimal täglicher
Injektion von 5-10 µg Exenatid einer Insulintherapie nicht unterlegen ist. Neu an
diesem Therapieansatz ist der zusätzlich günstige Einfluss einer Stimulation des GLP-1-Rezeptors
auf das Insulinsekretionsmuster, das Insulin-Glukagon-Verhältnis, das Körpergewicht
und möglicherweise auch die b-Zelldichte im Pankreas. Eine breite klinische Anwendung
von Exenatid wird aber auch wesentlich von der Verträglichkeit, einer möglichen Immunogenität
und der Patientencompliance abhängig sein. Zudem muss die Indikation für Exenatid
in der primären Behandlung des Typ-2-Diabetes sowie die prognostische Bedeutung dieses
neuartigen Therapieansatzes in weiteren kontrollierten Studien untersucht werden.
Summary
The incretin hormone glucagon-like peptide 1 (GLP-1) is being synthesized from L-cells
in the gut and enhances glucose-induced insulin secretion. Metabolic control of type
2 diabetic patients can be markedly improved by additional administration of GLP-1,
however, this peptide is almost immediately degraded and therefore has little clinical
value. The synthetic GLP-1 agonist exenatide underlies a different metabolism and
has recently been approved by the U.S. Food and Drug Administration for the adjunctive
treatment of patients with type 2 diabetes who are suboptimally controlled with metformin
and/or sulfonylurea. First controlled clinical trials provided evidence that glycaemic
control under exenatide administered twice daily in a dose of 5 - 10 µg was not inferior
to conventional insulin therapy. Novel aspects in the treatment of type 2 diabetes
by GLP-1 receptor stimulation further include its influence on the insulin secretory
pattern, insulin/glucagon ratio, body weight and possibly even pancreatic beta cell
mass. However, a general application of exenatide in the treatment of type 2 diabetes
will also largely depend on the therapy behavior of patients, a possible immunogenicity
and the rate of adverse events. Furthermore, a possible indication for exenatide as
first-line therapy of type 2 diabetes and the prognostic relevance of this novel therapeutic
approach have yet to be defined.
Schlüsselwörter
Antidiabetische Therapie - Diabetes mellitus - Exenatid - GLP-1 - Insulin-Glukagon
Verhältnis - Insulinsekretionsmuster - Inkretine
Key words
Antidiabetic therapy - Diabetes mellitus - Exenatide - GLP-1 - Insulin/glucagon ratio
- Insulin secretory pattern - Incretins
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Dr. med. Hannes Reuter
Klinik III für Innere Medizin, Universität zu Köln
Joseph-Stelzmann-Straße 9
50924 Köln
Telefon: 0221/4785403
Fax: 0221/4786550
eMail: Hannes.Reuter@koeln.de
