Neue Wege bei Typ-2-Diabetes – Insulin plus GLP-1-Rezeptoragonisten

Trotz neuer Therapieoptionen und moderner Insuline bleibt die Therapie des Typ-2-Diabetes eine Herausforderung, insbesondere bei Patienten mit Adipositas. Oft ist es schwierig, die strengen HbA_1c-Zielwerte zu erreichen, und selbst wenn es gelingt, ist die HbA_1c-Senkung nicht selten durch Gewichtszunahme und Häufung von Hypoglykämien erkauft. Neue Therapiestrategien sind deshalb gerade für das problematische Patientensegment mit Adipositas, Insulinresistenz und inadäquat erhöhtem HbA_1c erforderlich. Aus pathophysiologischer Sicht ist die Kombinationstherapie mit Insulin und Glukagon-like-Peptide-1(GLP-1)-Rezeptoragonisten sinnvoll, wenngleich harte klinische Daten zur Reduktion mikro- und makrosvaskulärer Komplikationen noch ausstehen. Diese Übersichtsarbeit fasst die verfügbaren Studiendaten zusammen und zeigt, dass die Kombination von Insulin plus GLP-1-Rezeptoragonist häufig mit einer erheblichen Stoffwechselverbesserung einhergeht und zusätzlich zur Gewichtsabnahme führt, bei nur geringem Anstieg des Hypoglykämierisikos, allerdings assoziiert mit dem bekannten gastrointestinalen Nebenwirkungsprofil der GLP-1-Rezeptoragonisten. Außerdem wird dargestellt, warum kurz wirksame GLP-1-Rezeptoragonisten, die mit einer deutlichen Senkung der postprandialen Blutzuckerspiegel assoziiert sind, eventuell besonders geeignet sind für die Kombination mit einem Basalinsulin, lang wirksame GLP-1-Rezeptoragonisten, die auf die Kontrolle des Nüchternblutzuckers abzielen, dagegen wahrscheinlich eher für die Kombination mit komplexeren Regimes wie der intensivierten konventionellen Insulintherapie, wenngleich auch hier klinische Vergleichsdaten fehlen.

Treatment of type 2 diabetes remains a challenge in spite of new treatment options and modern types of insulin, in particular for obese subjects. It is frequently difficult to achieve strict HbA_1c targets, and even in case of success this frequently happens at the expense of weight gain and an increased risk of hypoglycemia. Therefore, new treatment strategies are needed in particular for the high risk patient population with obesity, insulin resistance and inadequately high HbA1c. From a pathophysiological perspective, it is reasonable to combine insulin and glucagon-like peptide 1 (GLP 1) receptor agonists, although hard clinical data regarding the reduction of micro- and macrovascular complications are still missing. This review summarizes the clinical data available and illustrates that combined treatment with insulin plus GLP-1 receptor agonist will frequently achieve improved glycemic control and results in weight loss, with only a slightly increased risk of hypoglycemia, but associated with the known gastrointestinal side effect profile of GLP-1 receptor agonists. Additionally, this review explains why short-acting GLP-1 receptor agonists that are associated with a marked decrease of postprandial blood glucose levels may be particularly suitable for a combination with basal insulin, whereas long-acting GLP-1 receptor agonists that primarily aim at fasting blood glucose control may be more suitable for a combination with more complex insulin regimens such as the intensified conventional insulin therapy, although comparative clinical data are also missing here.

Key words

GLP-1 receptor agonist - insulin - exenatide - liraglutide - lixisenatide

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