Gut hormone polyagonists for the treatment of type 2 diabetes

Sara J. Brandt, Anna Götz, Matthias H. Tschöp, Timo D. Müller

Research output: Contribution to journalArticlepeer-review

91 Scopus citations


Chemical derivatives of the gut-derived peptide hormone glucagon-like peptide 1 (GLP-1) are among the best-in-class pharmacotherapies to treat obesity and type 2 diabetes. However, GLP-1 analogs have modest weight lowering capacity, in the range of 5–10%, and the therapeutic window is hampered by dose-dependent side effects. Over the last few years, a new concept has emerged: combining the beneficial effects of several key metabolic hormones into a single molecular entity. Several unimolecular GLP-1-based polyagonists have shown superior metabolic action compared to GLP-1 monotherapies. In this review article, we highlight the history of polyagonists targeting the receptors for GLP-1, GIP and glucagon, and discuss recent progress in expanding of this concept to now allow targeted delivery of nuclear hormones via GLP-1 and other gut hormones, as a novel approach towards more personalized pharmacotherapies.

Original languageEnglish
Pages (from-to)190-201
Number of pages12
StatePublished - Feb 2018


  • GLP-1/Glucagon Co-agonism
  • Gip
  • Polypharmacology
  • Type 2 diabetes


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