Zusammenfassung
Exenatide 1 × wöchentlich (Exenatide QW) ist eine neue Formulierung des Wirkstoffs
Exenatide, die durch eine Mikrospheren-Technologie ein sehr langsames Anfluten durch
ein langsam biodegradierbares Polymer, das als Träger von Exenatide fungiert, ermöglicht.
Dadurch ändern sich sowohl das Wirkungs- als auch das Nebenwirkungsprofil im Vergleich
zur kurzwirksamen Rezeptorstimulation mit herkömmlichem Exenatide. Studien konnten
eine stärkere Senkung der Nüchternblutzuckerwerte und des HbA1c durch Dauerstimulation am GLP-1-Rezeptor zeigen. Mit Metformin als Basistherapie
führte Exenatide QW zu einer überlegenen mittleren HbA1c -Senkung von 1,5 % bzw. 1,9 %, im Vergleich zu Exenatide 2 × tgl. (HbA1c – 1,0 %), Sitagliptin (HbA1c – 0,9 %), Pioglitazon (HbA1c – 1,2 %) oder Insulin Glargin (HbA1c – 1,3 %). Aufgrund einer geringeren Hemmwirkung auf die Magenentleerung ist dagegen
die postprandiale Glukoseabsenkung etwas weniger ausgeprägt als unter herkömmlichem
Exenatide, dafür ist die gastrointestinale Nebenwirkungsrate um etwa ⅓ (20 % versus
35 %) geringer. Zusätzlich wurde in allen Studien eine relevante mittlere Gewichtsabnahme
erreicht (von – 2,3 bis – 3,7 kg). Darüber hinaus konnten positive Effekte auf den
Blutdruck, das Lipidprofil und andere kardiovaskuläre Risikofaktoren beobachtet werden.
Deshalb ist eine kardiovaskuläre Outcome-Studie angelaufen, deren Daten in den nächsten
Jahren zu erwarten sind. Die bisherigen klinischen Studiendaten belegen, dass Exenatide QW
eine nützliche Therapieoption bei übergewichtigen, schlecht eingestellten Patienten
mit Typ-2-Diabetes nach Metformin darstellt, wenngleich sich Exenatide QW noch im
klinischen Alltag und in Langzeitstudien bewähren muss.
Abstract
Exenatide once weekly (exenatide QW) is a new dosage form of the active drug exenatide.
Exenatide QW’s microsphere technology enables very slow release due to the use of
a slowly biodegradable polymer as the exenatide carrier. This changes both the effect
and adverse effect profiles versus the short-acting receptor stimulation produced
by exenatide two times daily. Long-term stimulation of GLP-1 receptors results in
superior lowering of fasting blood glucose levels and HbA1c . In subjects on first-line treatment with metformin, exenatide QW produced superior
HbA1c reduction, with mean HbA1c reductions of 1.5–1.9 % versus exenatide two times daily (HbA1c – 1.0 %), sitagliptin (HbA1c – 0.9 %), pioglitazone (HbA1c – 1.2 %) and insulin glargine (HbA1c – 1.3 %). Because of the less pronounced inhibition of gastric emptying, postprandial
glycemia reduction is somewhat less effective than with conventional exenatide. Against
that, gastrointestinal toxicity is reduced by about one-third (20 % versus 35 %).
In addition, a relevant loss in mean weight (ranging from 2.3 to 3.7 kg) was seen
in all studies. Benefits were also documented for blood pressure, lipid profiles and
other cardiovascular risk factors. A cardiovascular outcome study has been launched
which is expected to generate data within the next few years. Clinical study data
available to date show that exenatide QW is a useful therapeutic option in subjects
with poorly controlled type 2 diabetes on metformin, even though the value of exenatide QW
has not yet been proven in real-life clinical practice and in long-term studies.
Schlüsselwörter
Exenatide - Exenatide QW - GLP-1-Rezeptoragonist - inkretinbasierte Therapie - Typ-2-Diabetes-Therapie
Key words
exenatide - exenatide QW - GLP-1 receptor agonist - incretin based therapy - type 2
diabetes therapy
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