At first sight it seems contradictory: glucagon raises glucose, the opposite of what metabolic research seeks. The key is balance. Besides releasing glucose from the liver, glucagon increases energy expenditure, promotes fat oxidation and reduces fat build-up in the liver.
If the same molecule combines it with enough GLP-1 agonism, the latter offsets the rise in glucose and the favourable effects of glucagon on energy balance remain. That is the basis of GLP-1/glucagon agonists (survodutide, mazdutide) and of the triple GLP-1/GIP/glucagon agonist (retatrutide).
Because of their action on the liver, these molecules are studied with particular interest in metabolic dysfunction-associated steatotic liver disease (MASLD/MASH), as well as in weight control.
The glucagon component is what sets survodutide, mazdutide and retatrutide apart from semaglutide and tirzepatide. Its proportion relative to GLP-1 defines each molecule's profile.
Related terms
Learn it in depth at the Peptide University
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