BethLabQueen said:

Holding genuinely reduces total burden rather than redistributing it, because the gastric-emptying component adapts.

I dislike how confidently this board tells people to push through. Incidence figures around 20 to 25% at the higher doses are class-typical, but the trials also had a discontinuation column, and "manageable with protocols" is not the same as manageable for everyone.

One concrete data point for the thread. 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.

Dr.AddMedPHL said:

I dislike how confidently this board tells people to push through.

Coming at Dr.AddMedPHL’s question from a different direction. 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.

A narrower follow-up, since the general answer is now clear:

What distinguishes the nausea you can titrate through from the nausea that means stop?

Closing the loop on my own question.

Update. It was not the dose, it was that I had stopped drinking anything because drinking made me feel full. Fixing that fixed most of it.