Survodutide (revision 4)

Survodutide (development code BI 456906) is an investigational peptide that agonises both the glucagon receptor and the GLP-1 receptor. It is under phase 3 evaluation for obesity and has been studied in metabolic dysfunction-associated steatohepatitis. It is not approved for use in any indication.^[1]

Unlike the GIP/GLP-1 pairing of tirzepatide, the glucagon/GLP-1 pairing sets two opposing glycaemic effects against each other deliberately. Glucagon-receptor agonism raises hepatic glucose output and energy expenditure; GLP-1 agonism lowers glucose and food intake. The design intent is to capture the energy-expenditure and hepatic-fat effects of the former while the latter dominates the net glycaemic balance.^[1]

Survodutide is a 29-residue acylated peptide derived from the glucagon sequence, with substitutions conferring GLP-1-receptor activity and a fatty-acid chain for albumin binding. Its natural template is oxyntomodulin, a product of proglucagon processing that is a weak agonist at both receptors — the existence of which is why the combination was thought physiologically coherent rather than merely chemically possible.^[1][2]

The potency ratio is the central design variable. Too much glucagon activity relative to GLP-1 activity raises fasting glucose; too little forfeits the energy-expenditure benefit that motivated the design. This is a fixed intramolecular property, so the balance must hold across the whole dose range rather than at one point in it.