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Glucagon receptor agonism might seem counterproductive for metabolic research given that glucose-elevating effect, but glucagon has additional effects that make selective agonism of research interest: Energy-expenditure increases through hepatic and adipose effects Lipolysis stimulation in adipose tissue Hepatic fat metabolism effects relevant to fatty-liver research Cardiac effects , including increased contractility The pharmacological insight behind Retatrutide's design is that glucagon receptor agonism combined with strong GLP-1 receptor agonism can leverage glucagon's energy-expenditure and lipolysis effects while GLP-1's glucose-lowering activity offsets glucagon's hyperglycemic effect