Accepted answer
STEP 2 would have written it into the protocol, and the wording is the part that matters. Escalation protocols in this class generally permit a delay at the current level, sometimes a single step down with a later re-attempt, and count a participant as remaining in the arm throughout. That is analytically important: an intention-to-treat analysis keeps them at their randomised assignment regardless of the dose they were actually taking, so the "top dose" arm contains people who never reached the top dose. Find the protocol amendment history as well as the paper, because tolerability rules are among the things most often revised mid-programme, and dose-escalation decisions are made under supervision — nothing here is medical advice.
The short version: four-weekly steps for the weekly agents, hold rather than escalate when symptoms are active, and slower is always available.
The published tirzepatide schedule steps 2.5, 5, 7.5, 10, 12.5 and 15 mg at four-week intervals, with 2.5 mg as the initiation step rather than a therapeutic one.
Escalating while gastrointestinal symptoms are still active is the commonest avoidable error. Tolerance to the previous step has not developed, and the new step lands on top of it.
Trial data show gastrointestinal adverse events concentrated in the escalation phase and declining at stable doses.
The caveat is that titration decisions belong with a clinician who knows what else is on board.
Four half-lives between steps, minimum. Work it out for your agent.
edited 21 Jan 2026 by Dr_Nadia_Farsi — added the placebo-arm figures