This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1 · go to the accepted answer.
Post #90 answers the question as asked. The question underneath it is different.
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.
I would want to see it done twice before believing it once.
I read post #89 twice before replying, because I had assumed the opposite.
Writing down the date, the dose and the site each week takes fifteen seconds and is the single most useful record anyone here keeps. Memory reconstructs a titration history that never happened.
A partial answer, offered because a partial answer beats none.
Following this. I have the same question and no better information than the first post.
The maximum studied dose is a fact about the trial and not a ceiling on the molecule. It is also the last point at which anything is known, which is the reason to treat it as one.
Coming back to post #92, because the follow-up matters more than the original answer.
Holding at a dose that is working is a legitimate position and it is not what the trial protocols did. The protocols escalated to a target because they were measuring the target dose, not finding each person's minimum.
That is my reading. Someone else read the same page differently and was reasonable.
There is no published evidence about slower escalation because nobody studied it. That means the trials support not going faster and are silent on going slower, which is a different claim from "slower is fine".
I checked the source rather than the summary, and they differ.
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.
If symptoms reset at each step, that is the expected pattern rather than a sign that the previous adaptation was imaginary. Every dose increase is a new exposure.
This follows post #100 rather than contradicting it.
Half steps are arithmetically simple and pharmacologically unstudied. They are not dangerous in any obvious way and they are also not what the evidence describes, and both halves of that should be said.
For what it is worth, the same held on the two occasions I checked.
Worth separating two things that post #98 runs together.
A missed dose in a weekly schedule is not a trough to chase. With a week-long half-life you are perturbing a slowly moving average, and the labelling for licensed products in this class says take it if the next dose is far enough away and skip it otherwise.
Adding it in case it saves somebody the afternoon it cost me.
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.
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.
Scoping that to what I have actually seen rather than what I have read.
Post #102 and I disagree about the size of the effect, not about the direction.
The starting dose in most of these programmes is a tolerance step and produces little effect by design. Judging the compound at the starting dose is judging the wrong thing.
Second-hand, so weight it accordingly.
Post #104 answers the question as asked. The question underneath it is different.
Going back down a step is not a failure and the trials allowed it. Several protocols permitted a return to the previous dose for tolerability and then a second attempt at the step.
Posting it because the silence on this was starting to look like agreement.
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.
It reads as pedantry until the day it does not.
If you are stepping up mainly because the schedule says so rather than because the current dose has stopped doing what you wanted, that is worth noticing before rather than afterwards.
Post #109 put the caveat in the right place and I want to underline it.
The four-week step is a trial convention, not a pharmacological constant. It is roughly four half-lives for a week-long half-life, which is the interval at which you are assessing a stable concentration rather than a rising one.
The disagreement above is smaller than it looks once the terms are fixed.
Building on post #109 rather than restating it.
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.
Nothing above should be read as advice about what anyone else should do.
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.
Post #113 and I disagree about the size of the effect, not about the direction.
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.
If that is already documented somewhere, ignore me and link it.
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.
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.
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.
That distinction has done more work for me than anything else in this category.
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.