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Practice · Dosing & titration

How the published trials escalated, tabulated side by side

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Solved by cannula_trace in post #2
Titrating on tolerability rather than on the calendar: some people escalate when they tolerate a dose well, others escalate on the prescribed schedule regardless. The published trials used a calendar-based schedule. Tolerability-based escalation has no formal evidence base but is not uncommon in practice.

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a.stephanopoulosTL3Regular3 Dec 2025#1

The question in the title: How the published trials escalated, tabulated side by side I will give what I have already checked below so nobody repeats it.

A question about technique rather than about dose.

I have been doing the same thing for 6 months and it works, and then I read one of the documentation pages here and realised I may have been reasoning from a misunderstanding the whole time. Nothing has gone wrong; I would just like to understand why it has not.

What I do, exactly, is described below. Please tell me which parts are load-bearing and which are superstition.

0 likes 8mo
CT
cannula_traceTL3Regular Solution23 Dec 2025#2

Titrating on tolerability rather than on the calendar: some people escalate when they tolerate a dose well, others escalate on the prescribed schedule regardless. The published trials used a calendar-based schedule. Tolerability-based escalation has no formal evidence base but is not uncommon in practice.

29 likes 7mo
GA
g.amankwahTL2 Moderator6 Jan 2026 · edited#3

Splitting a weekly dose in two: the pharmacokinetic argument against is that you want the benefit of long half-life, which gives a slowly changing plasma level from a weekly dosing schedule. Splitting it flattens the curve further but loses the convenience of once-weekly dosing. The trade-off is convenience versus a slightly flatter concentration curve.

14 likes 7mo
OF
outline_firstTL3Wiki editor19 Jan 2026#4

Dose equivalence between different incretin analogues is a weak concept. The molecules differ in structure, half-life, receptor selectivity, and in what has been studied clinically. One mg of semaglutide is not equivalent to one mg of something else in any meaningful sense.

20 likes 6mo
CC
c.castellanosTL2 Moderator31 Jan 2026#5
outline_first, post #4: Dose equivalence between different incretin analogues is a weak concept. The molecules differ in structure, half-life, receptor selectivity, and in what has been studied clinically. One mg of semaglutide is not equivalent to one mg of something else in any meaningful sense. Go to post

The four-week escalation interval is a convention from the pivotal trials, not a pharmacological constant. The pharmacological argument is that with a week-long half-life, four weeks approaches steady state and you can assess the dose fairly. That is an argument for not going faster. It is not an argument against going slower.

9 likes in reply to #4 6mo
NE
n.ekstromTL2Regular11 Feb 2026#6

Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up.

2 likes 5mo
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s.vukovicTL221 Feb 2026#7
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steady_stateTL3Regular3 Mar 2026#8

post #7 answers the question as asked. The question underneath it is different.

How the published trials escalated: they used specific step sizes and intervals. The STEP programme used a particular cadence; the SURPASS and SURMOUNT programmes used slightly different ones. Reading them side by side shows the variation is real but small.

27 likes 5mo
BT
b.teixeiraTL2 Moderator13 Mar 2026#9

The arithmetic of an intermediate dose: if the label says 1.0 mg and 2.0 mg, a dose strictly between them is off-label by definition. Some people compute it anyway. The reasoning is pharmacological — e.g., "I will split the difference between steps" — but it is reasoning from theory, not from evidence.

13 likes 5mo
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