Glucagon Receptor

The glucagon receptor (GCGR) is a G-protein-coupled receptor expressed primarily on hepatocytes and adipocytes. Activation drives hepatic glucose output and adipocyte lipolysis — the classic ‘fasting / mobilization’ signal opposite to insulin.

In obesity research, partial GCGR agonism is being studied as an additional mechanism for weight loss because it raises energy expenditure without proportionally raising glucose output (especially when paired with GLP-1 agonism, which suppresses the glucose-output side). Retatrutide is the most-studied triple agonist (GLP-1 + GIP + glucagon) currently in late-phase trials.

Survodutide and mazdutide are additional dual or triple agonist candidates active in the GCGR space, alongside the more-established tirzepatide.