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Adipositas - Ursachen, Folgeerkrankungen, Therapie 2018; 12(02): 76-83
DOI: 10.1055/s-0038-1654054
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Polypharmakologie als ein neuer Ansatz zur Präzisionsmedizin in der Adipositas- und Diabetestherapie

Polypharmacology as a novel approach towards precision medicine in the therapy of obesity and diabetes
S. Jall
1   Institut für Diabetes und Adipositas, Helmholtz Diabetes Center, Helmholtz Zentrum München
2   Lehrstuhl für Stoffwechselerkrankungen, Fakultät für Medizin, Technische Universität München
,
A. Götz
1   Institut für Diabetes und Adipositas, Helmholtz Diabetes Center, Helmholtz Zentrum München
3   Institut für Diabetes und Regeneration, Helmholtz Diabetes Center, Helmholtz Zentrum München
4   Medizinische Klinik I – Kardiologie, Pneumologie, Angiologie und Internistische Intensivmedizin
,
M. H. Tschöp
1   Institut für Diabetes und Adipositas, Helmholtz Diabetes Center, Helmholtz Zentrum München
2   Lehrstuhl für Stoffwechselerkrankungen, Fakultät für Medizin, Technische Universität München
5   Deutsches Zentrum für Diabetesforschung, Oberschleißheim
,
T. D. Müller
1   Institut für Diabetes und Adipositas, Helmholtz Diabetes Center, Helmholtz Zentrum München
5   Deutsches Zentrum für Diabetesforschung, Oberschleißheim
› Author Affiliations
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Publication History

Publication Date:
04 May 2018 (online)

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Zusammenfassung

Die weltweite Prävalenz von morbid gesteigertem Körpergewicht hat im 21. Jahrhundert epidemische Ausmaße angenommen. Adipositas gehört zu den wichtigsten Risikofaktoren für die Entstehung von Diabetes mellitus Typ 2, kardiovaskulären Erkrankungen und bestimmten Tumorleiden. Die Entwicklung neuer individueller pharmakologischer Therapieoptionen ist von größtem gesellschaftlichen Interesse, um der wachsenden Belastung unserer Gesundheitssysteme wirksam zu begegnen. Konservative Behandlungen, die beispielsweise auf eine Lebensstiländerung abzielen, sind nur unzureichend erfolgreich und derzeit verfügbare pharmakologische Therapieoptionen sind bislang nur wenig effektiv und/oder haben gravierende Nebenwirkungen. Einzelne Wirkstoffe, wie etwa Orlistat, waren bislang nicht in der Lage der steigenden Adipositaspandemie entgegenzuwirken. Ein vielversprechender neuer Ansatz ist es, die Wirkung verschiedener Schlüsselhormone in einem einzigen hochwirksamen Biomolekül zu vereinen. Verschiedene solcher Polyagonisten mit Multihormonwirkung befinden sich derzeit in klinischer Evaluation. Dazu gehört u.a. ein dualer Agonist mit Aktivität an den Rezeptoren für das Glukagon-ähnliche Peptid 1 (GLP-1) und Glukagon, ein dualer Agonist an den Rezeptoren für GLP-1 und das glukoseabhängige insulinotrope Polypeptid (GIP) sowie ein Triagonist mit Aktivität an den Rezeptoren für GLP-1, GIP und Glukagon. erfolgreich und derzeit verfügbare pharmakologische Therapieoptionen sind bislang nur wenig effektiv und/oder haben gravierende Nebenwirkungen. Einzelne Wirkstoffe, wie etwa Orlistat, waren bislang nicht in der Lage der steigenden Adipositaspandemie entgegenzuwirken. Ein vielversprechender neuer Ansatz ist es, die Wirkung verschiedener Schlüsselhormone in einem einzigen hochwirksamen Biomolekül zu vereinen. Verschiedene solcher Polyagonisten mit Multihormonwirkung befinden sich derzeit in klinischer Evaluation. Dazu gehört u.a. ein dualer Agonist mit Aktivität an den Rezeptoren für das Glukagon-ähnliche Peptid 1 (GLP-1) und Glukagon, ein dualer Agonist an den Rezeptoren für GLP-1 und das glukoseabhängige insulinotrope Polypeptid (GIP) sowie ein Triagonist mit Aktivität an den Rezeptoren für GLP-1, GIP und Glukagon.

Summary

The obesity epidemic is one of the biggest health problems of our society. Obese patients show an increased risk for developing many medical problems, including type 2 diabetes mellitus, cardiovascular disease and cancer. The development of individualized pharmacological treatment options is urgently needed for sustained weight loss and an overall improvement of the general health. Conservative, nonpharmacological treatment options, including lifestyle changes in diet and physical activity, as well as currently available pharmacological interventions are often ineffective and have undesirable adverse effects. Approved anti-obesity medication, like Orlistat, have so far been unsuccessful to sustainably decrease excess body weight. A novel concept is to combine the beneficial effect of several independent hormones in a single hormone entity. Several of such polyagonists are currently under clinical evaluation. Beneficial effects on body weight and glycemic control have been demonstrated for single hormone polyagonists targeting the receptors for GLP1 and glucagon, GLP-1 and GIP and also for a molecule targeting the receptors for GLP-1, GIP and glucagon.

Schlüsselwörter

Multihormonbehandlung - Pharmakologie - Polyagonismus - Präzisionsmedizin - Kombinationswirkstoffe

Keywords

Multihormone treatment - Pharmacology - Polyagonism - Precision medicine - Combination medication
 

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