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Diabetologie und Stoffwechsel 2016; 11(06): 398-417
DOI: 10.1055/s-0042-118174
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Dulaglutid: GLP-1-Rezeptoragonist zur einmal wöchentlichen Therapie des Typ-2-Diabetes

Dulaglutide: A GLP-1 Receptor Agonist for Once Weekly Treatment of Type 2 Diabetes
E. Heitmann
1   Medizinische Abteilung – Diabetes, Lilly Deutschland GmbH, Bad Homburg, Deutschland
,
H. Jung
1   Medizinische Abteilung – Diabetes, Lilly Deutschland GmbH, Bad Homburg, Deutschland
,
N. Schloot
1   Medizinische Abteilung – Diabetes, Lilly Deutschland GmbH, Bad Homburg, Deutschland
,
I. Pavo
2   Medizinische Abteilung – Diabetes, Eli Lilly GesmbH, Wien, Österreich
,
T. Forst
3   Medical Sciences, Profil Mainz GmbH und Co KG, Mainz, Deutschland
,
M. Trautmann
4   Diabetes Research, Consultant, Hamburg, Deutschland
,
G. Schernthaner
5   1. Medizinische Abteilung Hospital, Krankenhaus Rudolfstiftung, Wien, Österreich
› Institutsangaben
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Publikationsverlauf

01. Juni 2016

23. September 2016

Publikationsdatum:
20. Dezember 2016 (online)

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Erratum zu diesem Artikel:

Dulaglutid: GLP-1-Rezeptoragonist zur einmal wöchentlichen Therapie des Typ-2-DiabetesDiabetologie und Stoffwechsel 2016; 11(06): E1-E1
DOI: 10.1055/s-0036-1585054

Zusammenfassung

Einleitung: Dulaglutid ist als einer der neuesten GLP-1-Rezeptoragonisten für die einmal wöchentliche Injektion zur Therapie des Typ-2-Diabetes zugelassen. Die Wirksamkeit und Verträglichkeit von Dulaglutid ist durch derzeit 7 publizierte Phase-3-Studien des AWARD-Studienprogramms belegt.

Methodik: Diese Übersichtsarbeit fasst die Ergebnisse zur Wirksamkeit und Verträglichkeit von Dulaglutid einmal wöchentlich aus den publizierten AWARD-Studien zusammen und diskutiert den Stellenwert von Dulaglutid im Kontext der GLP-1-Rezeptoragonistenklasse bzw. anderer möglicher Therapieoptionen bei Typ-2-Diabetes.

Ergebnisse: Die AWARD-Studien mit insgesamt 5470 Patienten, davon 3375 mit Dulaglutid einmal wöchentlich behandelt, belegen die Wirksamkeit und Verträglichkeit von Dulaglutid in Kombination mit Metformin und/oder anderen Antidiabetika sowie in Monotherapie. Bei der HbA1c-Senkung war Dulaglutid in der in Deutschland üblichen 1,5-mg-Standarddosierung bei 6 der 7 Studien (AWARD-1 – 5, AWARD-8) der jeweiligen Vergleichssubstanz (Exenatide 2 × täglich, Insulin Glargin, Metformin, Sitagliptin) bzw. Plazebo überlegen und in der AWARD-6-Studie als erster wöchentlich injizierter GLP-1-Rezeptoragonist dem 1 × täglich zu injizierenden Liraglutid 1,8 mg nicht unterlegen. Wie bei allen GLP-1-Rezeptoragonisten waren Übelkeit, Durchfall und Erbrechen – meist in den ersten 2 Behandlungswochen – die häufigsten Nebenwirkungen. Die Hypoglykämieraten waren gering, und in allen Studien wurde zum Zeitpunkt des primären Studienziels mit der 1,5-mg-Dosierung eine mittlere Gewichtsreduktion von etwa 1 – 3 kg erreicht. Bei Betrachtung eines kombinierten Endpunktes (HbA1c < 7 % ohne Hypoglykämien oder Gewichtszunahme) zeigte Dulaglutid im Vergleich zu Exenatide 2 × täglich oder Insulin Glargin ein günstigeres Nutzen-Risiko-Profil; in indirekten „Bridging“-Vergleichsanalysen war dies auch gegenüber Sulfonylharnstoffen der Fall.

Schlussfolgerung: Das Wirksamkeits- und Verträglichkeitsprofil, kombiniert mit der einmal wöchentlichen Anwendung, macht Dulaglutid zu einer relevanten Behandlungsoption innerhalb der Klasse der GLP-1-Rezeptoragonisten. Therapieentscheidungen bei Typ-2-Diabetes, insbesondere beim Übergang zur injektablen Therapie, berücksichtigen neben der glykämischen Einstellung gemäß den Leitlinien zunehmend individuelle Bedürfnisse, Begleiterkrankungen und Präferenzen des Patienten. Die einzelnen GLP-1-Rezeptoragonisten sollten aufgrund der Unterschiede zwischen den Substanzen daher individuell betrachtet werden.

Abstract

Introduction: Dulaglutide is one of the most recent glucagon-like peptide 1 (GLP-1) receptor agonists and has been approved for once weekly injection in the treatment of type 2 diabetes. The efficacy and safety of dulaglutide have been shown in currently 7 published phase-3 studies of the AWARD study program.

Methods: This review summarizes the efficacy and safety results of the published AWARD studies and discusses the role of dulaglutide once weekly in the context of the GLP-1 receptor agonist class and other possible treatment options in type 2 diabetes.

Results: The AWARD studies had a total of 5470 patients, including 3375 patients treated with dulaglutide once weekly, and show the efficacy and safety of dulaglutide in combination with metformin and/or other antihyperglycemic treatments, as well as in monotherapy. In 6 of the 7 studies (AWARD-1 – 5, AWARD-8), the decrease in HbA1c achieved with the 1.5 mg standard dose of dulaglutide commonly used in Germany was superior to the respective comparator used (exenatide twice daily, insulin glargine, metformin, sitagliptin) or placebo. In the AWARD-6 study, dulaglutide 1.5 mg once weekly was the first weekly GLP-1 receptor agonist shown to be non-inferior to liraglutide 1.8 mg injected once daily. As with all GLP-1 receptor agonists, nausea, diarrhea and vomiting – usually occurring during the first 2 weeks of treatment – were the most common adverse effects. Hypoglycemia rates were low, and in all studies at primary study endpoint a mean weight reduction of approximately 1 – 3 kg was observed with the 1.5 mg dose. When looking at a combined endpoint (HbA1c < 7 % with no hypoglycemia or weight gain), dulaglutide was associated with a more advantageous benefit risk profile compared with exenatide twice daily or insulin glargine; in indirect, comparative „bridging“ analyses this was also the case for the comparison against sulfonylureas.

Conclusions: The efficacy and safety profile, together with once-weekly administration, make dulaglutide a relevant treatment option within the class of GLP-1 receptor agonists. Treatment decisions for type 2 diabetes, in particular when transitioning to injectable antihyperglycemic treatment, increasingly consider patients’ specific requirements, comorbidities and preferences in addition to the adjustment of glycemic control as per guidelines. Each GLP-1 receptor agonist should therefore be considered individually, due to the differences between these agents.

Schlüsselwörter

AWARD - Dulaglutid - GLP-1-Rezeptoragonist - klinische Studien - Typ-2-Diabetes - Versorgungsforschung

Key words

AWARD - dulaglutide - GLP-1 receptor agonist - dlinical trials - type 2 diabetes - patient care
 

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