Glucagon-like peptide-1 in diabetes care: Can glycaemic control be achieved without nausea and vomiting?

Tito Borner, Ian C. Tinsley, Robert P. Doyle, Matthew R. Hayes, Bart C. De Jonghe

Research output: Contribution to journalReview articlepeer-review


Introduced less than two decades ago, glucagon-like peptide-1 receptor agonists rapidly reshaped the field of Type 2 diabetes mellitus (T2DM) care by providing glycaemic control in tandem with weight loss. However, FDA-approved GLP-1 receptor agonists are often accompanied by nausea and emesis and, in some lean T2DM patients, by undesired anorexia. Importantly, the hypophagic and emetic effects of GLP-1 receptor agonists are caused by activation of central GLP-1 receptors. This review summarizes two different approaches to mitigate the incidence and severity of nausea and emesis related to GLP-1 receptor agonists: conjugation with vitamin B12, or related corrin ring-containing compounds (‘corrination’), and development of dual agonists of GLP-1 receptors with glucose-dependent insulinotropic polypeptide (GIP). Such approaches could lead to the generation of GLP-1 receptor agonists with improved therapeutic efficacy, thus decreasing treatment attrition, increasing patient compliance and extending treatment to a broader population of T2DM patients. The data reviewed show that it is possible to pharmacologically separate the emetic effects of GLP-1 receptor agonists from their glucoregulatory action.

Original languageEnglish (US)
JournalBritish Journal of Pharmacology
StateAccepted/In press - 2021


  • area postrema
  • cobinamide
  • corrination
  • diabetes mellitus
  • emesis
  • GIPR/GLP-1R dual agonists
  • glucose-dependent insulinotropic polypeptide
  • hindbrain
  • side effects
  • tirzepatide
  • vitamin B

ASJC Scopus subject areas

  • Pharmacology


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