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Practice · Dosing & titration

[2026 update] Dose numbers across compounds are not on the same scale

KV
k.vanheckeTL2 Moderator1 Jan 2025#1

On the subject in the title: Dose numbers across compounds are not on the same scale Working notes rather than a conclusion.

I have read the maintained page on this and I still have a gap, so I am asking rather than guessing.

Context: tirzepatide, 22 weeks in, currently at a dose I reached by the standard four-week steps. Everything below is my own record rather than anything a clinician told me.

The specific question is the one in the title. What I have already checked: the labelling summary on the relevant documentation page, the two most-linked topics in this subcategory, and my own notes from the last 10 weeks. What I could not find is whether the answer changes at higher doses or whether it is the same arithmetic throughout.

If the answer is "it depends", I would rather know what it depends on than be given a number.

3 likes 19mo
BV
bias_varianceTL4Biostatistician19 Jan 2025#2

Holding a dose indefinitely: the trials did not study indefinite holding at a non-maximum dose. The trials escalated to a target and then held that. What happens if you stay at an intermediate dose for years is not formally studied and extrapolation is the best available reasoning.

6 likes 18mo
HD
h.delgadoTL2 Moderator1 Feb 2025#3

For anyone arriving from a search: the marked solution above is the direct answer, and the replies underneath it add the caveats that make it safe to use.

17 likes 18mo
IT
impurity_tableTL3Analytical chemist13 Feb 2025#4
bias_variance, post #2: Holding a dose indefinitely: the trials did not study indefinite holding at a non-maximum dose. The trials escalated to a target and then held that. What happens if you stay at an intermediate dose for years is not formally studied and extrapolation is the best available reasoning. Go to post

On post #2 — agreed on the reasoning, with one qualification.

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.

32 likes in reply to #2 17mo
NL
n.laurentTL2 Moderator24 Feb 2025#5
impurity_table, post #4: On post #2 — agreed on the reasoning, with one qualification. 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… Go to post

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.

0 likes in reply to #4 17mo
CR
compounding_ruthTL4Pharmacist6 Mar 2025#6

When a dose reduction is the correct response to a side effect: if a side effect is dose-dependent (nausea, constipation, injection discomfort), reducing the dose is a reasonable response. If the side effect is not dose-dependent (e.g., hypoglycemia with insulin), dose reduction does not address the issue.

3 likes 17mo
VB
va.baptistaTL216 Mar 2025#7
TV
t.vasquezTL4 Moderator25 Mar 2025#8
Staff post. Actions described here are recorded in the public moderation log and may be challenged in Meta.

Worth separating two things that post #4 runs together.

Two things before anyone answers the substance.

First, the context in the first post is clear and specific. Second, the question is framed so that an answer can actually address it. Both are the norm here and both matter more than they sound.

24 likes 16mo
HF
h.friskTL2 Moderator4 Apr 2025#9

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.

0 likes 16mo
GP
g.pemberton_ukTL3Regional · UK12 Apr 2025#10

Coming back to post #8, because the follow-up matters more than the original answer.

Two things before anyone answers the substance.

First, the context in the first post is clear and specific. Second, the question is framed so that an answer can actually address it. Both are the norm here and both matter more than they sound.

1 like 15mo
SF
sterile_fileTL321 Apr 2025#11
CM
c.marchettiTL2 Moderator30 Apr 2025#12
sterile_file, post #11: Stepping down deliberately: the withdrawal trials show that stopping is followed by regain. The step-down literature is thinner. The conservative assumption is that stepping down is followed by some regain, with the magnitude unknown. Go to post

post #11 answers the question as asked. The question underneath it is different.

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 in reply to #11 15mo
AS
a.stephanopoulosTL3Regular8 May 2025#13

Coming back to post #11, because the follow-up matters more than the original answer.

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.

2 likes 15mo
LC
l.cabreraTL2 Moderator16 May 2025#14

For anyone arriving from a search: the marked solution above is the direct answer, and the replies underneath it add the caveats that make it safe to use.

0 likes 14mo
ED
e.dalgleishTL3Regular24 May 2025#15
k.vanhecke, post #1: On the subject in the title: Dose numbers across compounds are not on the same scale Working notes rather than a conclusion. I have read the maintained page on this and I still have a gap, so I am asking rather than guessing. Context: tirzepatide, 22 weeks in, currently at a dose I reached by the standard four-week steps. Everything… Go to post

Reaching a dose and staying there for a year: the question of whether a stable dose remains effective over years is mostly answered by the withdrawal trials and by real-world reports. The dose does not seem to stop working, but the longest trials are not indefinitely long.

0 likes in reply to #1 14mo
SS
s.salgadoTL2 Moderator1 Jun 2025#16
a.stephanopoulos, post #13: Coming back to post #11, because the follow-up matters more than the original answer. 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… 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.

20 likes in reply to #13 14mo
D
DOdendaalTL3Regular9 Jun 2025#17

I read post #15 twice before replying, because I had assumed the opposite.

Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.

The correction was fair and I had been repeating something I had not checked carefully enough.

5 likes 14mo
MB
ma.balogunTL2 Moderator16 Jun 2025#18

This follows post #15 rather than contradicting it.

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.

0 likes 13mo
VK
v.klausenTL3Regular24 Jun 2025#19

On post #15 — agreed on the reasoning, with one qualification.

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 13mo

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