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.
Keywords: Blood glucose; Glucagon-like peptide 1; Glucose-dependent insulinotropic peptide; Overweight; Weight loss.