Follow-up: Why "dose equivalence" between different incretin analogues is a weak concept

Asking directly, because I could not find a straight answer: Why "dose equivalence" between different incretin analogues is a weak concept

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

Context: semaglutide, 9 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 14 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.

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.

Post #2 is right about the mechanism and I think understates the practical bit.

Concentration and dose get conflated constantly in this subcategory. Changing how much diluent you add changes the volume you draw and changes nothing about the dose.

Worth checking against a second source before it gets quoted onward.

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

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.

Happy to expand any of that if it is the useful part.

Adding the measurement that post #2 says would settle it.

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".

This is where my knowledge stops and I would rather mark the edge than blur it.

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.

I had written a reply contradicting post #4 and deleted it. Here is what survived.

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.

Someone will know this better than I do and I hope they say so.

Saving this. It is the version I will quote when the question comes round again.

Dose and effect are not linear across the studied range for every compound in this class. Assuming a doubled dose gives a doubled effect is the reasoning error behind most disappointment.

I would put this at better than even and not much better.

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.

Old habit: I write down the expected answer before I calculate it.