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

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

A narrow question about Dose numbers across compounds, deliberately narrow, because the broad version has been asked here four times and produced four long threads and no answer.

One question, stated units, stated method, and what I have already ruled out.

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.

The evidence for this is thinner than the way I have phrased it suggests.

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.

The opening post describes the usual case. This is about the unusual one.

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.

That has been true for the cases I have seen and I have not seen many.

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.

I have changed my mind on this once already, so take it as current rather than settled.

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.

On post #4 — agreed on the reasoning, with one qualification.

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.

That is what I would do. It may not be what is correct.

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.

Noted, and I have changed what I was going to do on the strength of it.

Narrowing post #9, because the general version has more than one answer.

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.

Post #12 and I disagree about the size of the effect, not about the direction.

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.

I would put a moderate confidence on that and no more.

Grateful for the specificity. Vague answers to this question are what sent me looking.