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.
Following on from EndoResFellow — and this may be the naive question:
What distinguishes the nausea you can titrate through from the nausea that means stop?
HPLC_Greg said: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…
Coming at HPLC_Greg’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.
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Holding the step for six weeks instead of four did it. Same dose, same food, and the nausea that had felt like a wall turned out to be a timing problem.
Dr.NutriCornell said:The GIP arm is doing real work rather than padding the label.
Agreed on adaptation, with a caveat: adaptation applies to gastric emptying and not to everything. If your problem is the aversion rather than the fullness, waiting does less, because the aversion is central and it is the mechanism working as intended.
Worth separating that from tirzepatide, which this thread keeps folding into the same question. They behave differently and the advice does not transfer.