title: Unimolecular Polypharmacy for Treatment of Diabetes and Obesity.
abstract: Many complex diseases have historically proven to be defiant to the best mono-therapeutic approaches. Several examples of combination therapies have largely overcome such challenges, notably for the treatment of severe hypertension and tuberculosis. Obesity and its consequences, such as type 2 diabetes, have proven to be equally resistant to therapeutic approaches based on single medicines. Proper management of type 2 diabetes often requires adjunctive medications, and the recent registration of a few compound mixtures has set the precedent for combinatorial treatment of obesity. On the other hand, double or triple therapeutic combinations are more difficult to advance to regulatory approval than single molecules. More recently, several classes of novel unimolecular combination therapeutics have emerged with superior efficacy than currently prescribed options and pose the potential to reverse obesity and type 2 diabetes. Here, we summarize the discovery, pre-clinical validation, and first clinical test of such peptide hormone poly-agonist drug candidates.
authors.affiliation: Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, Munich 85748, Germany; Division of Metabolic Diseases, Technische Universität München, Munich 85748, Germany; German Center for Diabetes Research (DZD), Neuherberg 85764, Germany. Electronic address: matthias.tschoep@helmholtz-muenchen.de.
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Tschöp
authors.affiliation: Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, Munich 85748, Germany; Division of Metabolic Diseases, Technische Universität München, Munich 85748, Germany; German Center for Diabetes Research (DZD), Neuherberg 85764, Germany.
authors.forename: Brian
authors.initials: B
authors.lastname: Finan
authors.affiliation: Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, Munich 85748, Germany; Division of Metabolic Diseases, Technische Universität München, Munich 85748, Germany; German Center for Diabetes Research (DZD), Neuherberg 85764, Germany.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Clemmensen
authors.affiliation: Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.
authors.forename: Vasily
authors.initials: V
authors.lastname: Gelfanov
authors.affiliation: Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45237, USA.
authors.forename: Diego
authors.initials: D
authors.lastname: Perez-Tilve
authors.affiliation: Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, Munich 85748, Germany; Division of Metabolic Diseases, Technische Universität München, Munich 85748, Germany; German Center for Diabetes Research (DZD), Neuherberg 85764, Germany.
authors.forename: Timo D
authors.initials: TD
authors.lastname: Müller
authors.affiliation: Department of Chemistry, Indiana University, Bloomington, IN 47405, USA. Electronic address: rdimarch@indiana.edu.
authors.forename: Richard D
authors.initials: RD
authors.lastname: DiMarchi
mesh_terms: D000595:Amino Acid Sequence; D050110:Bariatric Surgery; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D009765:Obesity / Q000188:drug therapy*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D019338:Polypharmacy
chemical_list: D010455:Peptides; D005934:Glucagon