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

Reporting something rather than asking about it, in case the pattern is useful to anyone else.

Over 12 weeks I logged this consistently: date, dose, time of day, and a simple severity score from 0 to 4 for each symptom. That is 93 data points, all self-reported, all unblinded, and collected by someone who knew what he expected to find. Treat it accordingly.

The reason I am posting is that my experience does not match the shape people usually describe here, and I would like to know whether that is unusual or whether the usual description is just the loudest version.

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.

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

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.

Worth separating two things that the opening post runs together.

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.

Picking up post #2: that is the part I would want checked first.

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.

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.

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

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.

I read post #8 twice before replying, because I had assumed the opposite.

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.

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.

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.