Practice · Dosing & titration

Holding a dose indefinitely: is there a documented downside?

Practice › Dosing & titration dose reduction missed dose semaglutide

h.falkTL2 Moderator7 Nov 2024#1

Holding a dose indefinitely: is there a documented downside? — that is the question, and I have not found it answered plainly anywhere I have looked.

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 21mo

owen.bradyTL4 Moderator25 Nov 2024#2

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Worth separating two things that the opening post runs together.

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 20mo

r.serranoTL2 Moderator8 Dec 2024#3

This follows post #2 rather than contradicting it.

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.

7 likes 20mo

peak_purityTL3Analytical chemist19 Dec 2024#4

owen.brady, post #2: Worth separating two things that the opening post runs together. 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. Go to post

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.

18 likes in reply to #2 19mo

b.demirTL2 Moderator30 Dec 2024#5

r.serrano, post #3: This follows post #2 rather than contradicting it. 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. Go to post

post #4 answers the question as asked. The question underneath it is different.

Micro-titration: the concept of increments smaller than the labelled steps. It has no evidence base from trials but is described by some people. The downside is that very small increments are hard to measure accurately with a syringe.

0 likes in reply to #3 19mo

s.bruunTL2 Moderator9 Jan 2025#6

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

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.

1 like 19mo

g.rasmussenTL2 Moderator19 Jan 2025#7

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.

11 likes 18mo

mira.patelTL4 Admin28 Jan 2025 · edited#8

peak_purity, post #4: 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… Go to post

Practical note that does not fit anywhere else. Whatever you conclude from this topic, write down what you did and when. The single most useful thing in your own records is not any individual result; it is that they are dated and consecutive.

24 likes in reply to #4 18mo

ro.zielinskiTL2 Moderator6 Feb 2025#9

g.rasmussen, post #7: 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. Go to post

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.

18 likes in reply to #7 18mo

priorauth_notesTL2Regular15 Feb 2025#10

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.

0 likes 17mo

m.ibarraTL2 Moderator23 Feb 2025#11

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 17mo

s.leclercTL4 Moderator4 Mar 2025#12

h.falk, post #1: Holding a dose indefinitely: is there a documented downside? — that is the question, and I have not found it answered plainly anywhere I have looked. 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… Go to post

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.

32 likes in reply to #1 17mo

l.salinasTL2 Moderator12 Mar 2025#13

Worth separating two things that post #9 runs together.

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.

16 likes 17mo

a.reyesTL4 Admin20 Mar 2025#14

Staff post. Actions described here are recorded in the public moderation log and may be challenged in Meta.

I disagree with the reply above, and I think the disagreement is substantive rather than terminological.

The distinction being drawn does not survive when you look at the published data for this specific question. I would be glad to be shown wrong on this, because the version I am arguing against is more convenient.

6 likes 16mo

j.steinerTL2 Moderator28 Mar 2025 · edited#15

b.demir, post #5: post #4 answers the question as asked. The question underneath it is different. Micro-titration: the concept of increments smaller than the labelled steps. It has no evidence base from trials but is described by some people. The downside is that very small increments are hard to measure accurately with a syringe. Go to post

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.

1 like in reply to #5 16mo

n.moreauTL2 Moderator5 Apr 2025#16

Picking up post #13: that is the part I would want checked first.

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.

0 likes in reply to #2 16mo

p.mbekiTL2 Moderator12 Apr 2025#17

Steady state means the plasma concentration is stable from dose to dose. That happens around 4 to 5 half-lives. Before that, the concentration is rising with each dose. Escalating before steady state means escalating on incomplete information about the dose you are on.

23 likes 16mo

b.solbergTL2 Moderator20 Apr 2025#18

10 likes 15mo

m.coelhoTL2 Moderator27 Apr 2025#19

I read post #17 twice before replying, because I had assumed the opposite.

33 likes 15mo

s.bergstromTL2 Moderator5 May 2025#20

This follows post #17 rather than contradicting it.

I disagree with the reply above, and I think the disagreement is substantive rather than terminological.

17 likes 15mo

b.restrepoTL212 May 2025#21

Collapsed as off-topic by two members at trust level 3 or above

PSkarbekTL3Regular19 May 2025#22

11 likes 14mo

k.agyemanTL2 Moderator27 May 2025#23

32 likes 14mo

buffer_marginTL3Regular3 Jun 2025#24

Worth separating two things that post #20 runs together.

0 likes in reply to #2 14mo

i.coelhoTL2 Moderator10 Jun 2025#25

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.

6 likes 14mo

c.dahlbergTL2 Moderator17 Jun 2025#26

16 likes 13mo

t.abubakarTL2 Moderator23 Jun 2025#27

post #26 answers the question as asked. The question underneath it is different.

0 likes 13mo

d.petrescuTL2 Moderator30 Jun 2025#28

s.bruun, post #6: On post #2 — agreed on the reasoning, with one qualification. 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… Go to post

On post #24 — agreed on the reasoning, with one qualification.

1 like in reply to #6 13mo

z.onwukaTL2 Moderator7 Jul 2025#29

This follows post #26 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.

10 likes in reply to #3 13mo

f.kimaniTL2 Moderator14 Jul 2025#30

I read post #28 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.

23 likes 12mo

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