This is the version of the explanation I wish somebody had given me, written down before I forget what confused me. It is about nausea, and it is deliberately narrow — everything I am not confident about is marked as such.
What is actually established
Holding genuinely reduces total burden rather than redistributing it, because the gastric-emptying component adapts. Receptor-level tachyphylaxis to the delayed-emptying effect develops over weeks while the central appetite effect persists, so the same dose is materially more comfortable at week six than at week two. A slower ladder therefore reaches the same dose with less cumulative nausea, not the same nausea spread thinner.
The condition it depends on
The meal advice is right and incomplete without the hydration point. People stop drinking because drinking makes them feel full, then attribute dehydration symptoms to the drug.
The practical version
Trial-level incidence runs roughly 20 to 25% for nausea at the higher dose tiers and 12 to 17% for diarrhoea, with most events mild to moderate and concentrated in the weeks after each escalation.
What I am not sure about
What I actually want to know is whether holding at a lower dose for longer actually reduces total side-effect burden or just spreads it out. Happy to be told the question itself is wrong.
— ChrisMacros · corrections welcome and will be edited into this post with credit