A reference post rather than a discussion. Corrections are the point; I would rather this be right than mine. It is about tirzepatide, and it is deliberately narrow — everything I am not confident about is marked as such.
What is actually established
The GIP arm is doing real work rather than padding the label. GIP receptor agonism appears to improve adipose insulin sensitivity and lipid handling, and — counter-intuitively — GIP signalling in the CNS reduces nausea rather than adding to it, which is why tolerability at high total agonism is better than the GLP-1-only comparison would predict. SURPASS-2 is the cleanest head-to-head: tirzepatide beat semaglutide 1mg at every dose tier.
The condition it depends on
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.
The practical version
Practical numbers: half-life about 5 days, steady state 3 to 4 weeks, ladder 2.5 / 5 / 7.5 / 10 / 12.5 / 15mg, and the maintenance doses with published data behind them are 5, 10 and 15mg.
What I am not sure about
What I am trying to establish is whether anyone has held 10mg long term rather than climbing, and what happened over the following year. Not looking for reassurance. Looking for the part I have got wrong.
— alex_tucson · corrections welcome and will be edited into this post with credit