Short answer first, then the reasoning. Steady state is faster than people expect: half-life about five days, so you are at plateau in roughly three to four weeks rather than five. That matters when you are deciding whether a dose step has finished expressing itself.

Dr.BariatricHTX said:

Steady state is faster than people expect: half-life about five days, so you are at plateau in roughly three to four weeks rather than five.

Agreed on the mechanism, with the caveat that the head-to-head used semaglutide 1mg, not 2.4mg. It is still the best direct evidence available, but it is not the comparison most people think they are citing.

MASHdoc_SA said:

Watching the glucagon co-agonists for the liver endpoints and finding almost nothing written about them that is not a press release.

True, though the ladder is longer and that is not a neutral detail — six dose steps means six opportunities to stall on the way up, and plenty of people never reach the dose the headline number came from.

Adding the clinical framing, because it changes how the question reads.

Glucagon receptor pharmacology in triple agonists (retatrutide), relevant to the glucagon co-agonists: the glucagon component is the most controversial because glucagon traditionally raises blood glucose. So why include it in an anti-obesity drug?

Key insight: glucagon increases energy expenditure (thermogenesis), promotes hepatic lipid oxidation, and reduces appetite through distinct CNS mechanisms. The hyperglycemic effect is counterbalanced by the GLP-1 component's insulin secretagogue action.

Net result: more weight loss through increased expenditure (glucagon) + decreased intake (GLP-1/GIP), with neutral or improved glycemia. An elegant pharmacological balancing act[1].