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Inkretinbasierte Diabetesmedikamente

Kardiovaskuläre Sicherheit bzw. kardiovaskulärer „Benefit“

Incretin-based diabetes drugs

Cardiovascular safety and “benefit”

  • Leitthema
  • Published:
Der Diabetologe Aims and scope

Zusammenfassung

Hintergrund

Die amerikanische FDA („U.S. Food and Drug Administration“) fordert seit 2008 für neue Antidiabetika die Durchführung kardiovaskulärer Sicherheitsstudien. Kardiale Sicherheit ist demzufolge eine Conditio sine qua non. Dieser Forderung haben wir die großen kardiovaskulären Phase-4-Endpunktstudien („cardiovascular outcome trials“, CVOT) zu verdanken, die für die neueren Antidiabetika, DPP-4-Inhibitoren (DPP: Dipeptidylpeptidase), GLP-1-Agonisten (GLP: „glucagon-like peptide“) und auch SGLT-2-Inhibitoren (SGLT: „sodium dependent glucose transporter“) durchgeführt wurden und werden.

Ziele und Methode

Insbesondere die inkretinbasierten Therapiekonzepte wurden hinsichtlich ihrer kardiovaskulären Sicherheit geprüft und wesentliche Daten hierzu und zu ihrer Effizienz zusammengestellt. Die Analyse schließt bewusst nicht nur die kardiovaskulären Endpunkte mit ein, sondern widmet sich auch dem über die Einstellung des Blutzuckerspiegels hinausgehenden zusätzlichen Endorgannutzen.

Ergebnisse

Die bisher veröffentlichten RCT („randomized controlled trial“) zum Thema inkretinbasierte Therapie und kardiovaskuläre Sicherheit zeigen mindestens keine Unterlegenheit gegenüber der Standardtherapie (Gliptine und Lixisenatid), im Fall von Liraglutid und Semaglutid sogar eine Überlegenheit im kombinierten Endpunkt MACE („major adverse cardiovascular events“). Damit bestätigten sich die Ergebnisse vorhergehender präklinischer Untersuchungen bezüglich eines potenziellen positiven Effekts – zumindest für die derzeit verfügbare Substanz Liraglutid. Für die 1‑mal wöchentlich zu verabreichenden Präparate Exenatid QW, Dulaglutid und Albiglutid liegen erste Daten aus klinischen Studienprogrammen vor, die Präsentation der umfassenden Ergebnisse der CVOT wird für Herbst 2017 bzw. 2019 erwartet.

Abstract

Background

Since 2008, the conductance of cardiovascular safety studies regarding new antidiabetic substances is mandatory and is considered by the U.S. Food and Drug Administration (FDA) as conditio sine qua non. This requirement led to cardiovascular outcome trials (CVOTs), which are or will be available for newer glucose-lowering substances, comprising DPP-4 inhibitors (DPP: dipeptidyl peptidase), GLP-1 receptor agonists (GLP: glucagon-like peptide), and SGLT-2 inhibitors (SGLT: sodium-dependent glucose transporter).

Objective and methods

In particular, the incretin-based therapeutic concepts were tested for their cardiovascular safety, and essential data on this and their efficacy were compiled. The analysis deliberately includes not only cardiovascular aspects but also other pleiotropic effects beyond blood glucose adjustment.

Results

Published results from randomized controlled trials on the subject of incretin-based therapy and cardiovascular safety shows noninferiority to standard treatment (gliptins and lixisenatide) and in the case of liraglutide and semaglutide, superiority regarding the combined endpoint MACE (major adverse cardiovascular events) was confirmed. With this, preclinical studies showing beneficial effects on the cardiovascular and endothelial systems have been confirmed—at least for the currently available substance liraglutide. Preliminary results from clinical trials are available for the once-weekly formulations exenatide QW, dulaglutide, and albiglutide; however, detailed results from the CVOTs are awaited in autumn 2017 and in 2019.

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Authors and Affiliations

  1. Herz- und Diabeteszentrum NRW, Diabeteszentrum, Ruhr-Universität Bochum, Georgstraße 11, 32545, Bad Oeynhausen, Deutschland

    Y. H. Lee-Barkey, B. Stratmann &  D. Tschöpe

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  1. Y. H. Lee-Barkey
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  2. B. Stratmann
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  3. D. Tschöpe
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Correspondence to D. Tschöpe.

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Interessenkonflikt

Y.H. Lee-Barkey erhielt Vortragshonorare von AstraZeneca, BMS, Boehringer Ingelheim, Lilly, MSD und Sanofi sowie Kongressgebühren von Boehringer Ingelheim und Lilly. B. Stratmann und gibt an, dass kein Interessenkonflikt besteht. D. Tschöpe erhielt Beraterhonorare von Amgen, AstraZeneca, Boehringer Ingelheim, Novo Nordisk und Servier sowie Vortragshonorare, Kongressgebühren und Reisekosten von AstraZeneca, Boehringer Ingelheim, Lilly, MSD, Novo Nordisk, Sanofi und Servier. Als Honorarverantwortlicher erhielt er Gelder für klinische Studien von AstraZeneca, Bayer, Lilly, Novo Nordisk und Sanofi.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Lee-Barkey, Y.H., Stratmann, B. & Tschöpe, D. Inkretinbasierte Diabetesmedikamente. Diabetologe 13, 498–504 (2017). https://doi.org/10.1007/s11428-017-0269-8

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