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[Incretin-based co- and tri-agonists : Innovative polypharmacology for the treatment of obesity and diabetes]
A Harger1,2, K Stemmer1,2, M H Tschöp2,3,4
1Institut für Diabetes und Adipositas, Helmholtz Diabetes Center (HDC), Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764, Neuherberg, Deutschland.
Background:
The worldwide rise in overweight and obesity is paralleled by an increasing prevalence of type-2 diabetes. Apart from bariatric surgery, treatment options to decrease body weight are often underwhelming. Innovative pharmacological options are required to cope with the global "diabesity" pandemic.
Objectives:
Particular novel pharmacological approaches are discussed, with a special focus on polyagonist-based pharmacotherapies.
Materials And Methods:
Articles on co- and tri-agonists for the treatment of obesity and diabetes are presented and discussed.
Results:
Unimolecular peptides have been developed for the treatment of obesity and type-2 diabetes. These peptides activate the receptors of multiple hormones and bundle their positive effects in one single molecule. In preclinical studies, polyagonists targeting the receptors for glucagon-like peptide-1 (GLP-1), glucagon, or glucose-dependent insulinotropic peptide (GIP) were promising to reduce body weight and blood glucose. GLP-1-mediated delivery of the nuclear hormones estrogen or dexamethasone also yielded beneficial effects in preclinical studies of obesity.
Conclusions:
Polyagonists represent an innovative strategy for the development of novel pharmacotherapies to treat obesity and diabetes.
![Assessment of Gastric Emptying in Non-obese Diabetic Mice Using a [13C]-octanoic Acid Breath Test](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F50301.jpg&w=3840&q=50)
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