Time to steady state after a dose increase

Body weight affects volume of distribution and therefore exposure at a fixed dose. Whether that translates into a dosing implication depends on the width of the therapeutic window.

Everything in post #15 holds. The case it does not cover is the one I have.

Metabolism for peptide drugs is proteolytic rather than hepatic in the usual sense, which is why the cytochrome interaction questions that dominate small-molecule pharmacology mostly do not apply.

Scoping that to what I have actually seen rather than what I have read.

A pharmacokinetic model fitted to trial data describes the population studied. Applying it to somebody outside the enrolled range is an extrapolation, and the model will not tell you it is.

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

Coming back to post #15, because the follow-up matters more than the original answer.

Loading doses are not used in this class and the pharmacokinetic reason is tolerability rather than efficacy. A loading dose would reach steady state faster and would be intolerable.

Half-life: semaglutide ≈ 165–184 hours (about a week). Tirzepatide ≈ 5 days. Liraglutide ≈ 13 hours. The half-life determines how much accumulation happens at steady state and how long it takes to clear after stopping.

I keep a log of this specifically because memory is unreliable about it.

Accumulation at steady state: with a week-long half-life, steady-state concentration is reached around 4 to 5 half-lives (about 4 to 5 weeks). Before that, concentration is rising with each dose. The clinical implication: escalating before 4 weeks means escalating before steady state.

Understood, and I withdraw the assumption I opened with.

Coming back to post #22, because the follow-up matters more than the original answer.

Individual variation: people vary in how quickly they absorb, distribute, metabolise, and excrete these compounds. That variation is partly genetic and partly due to individual biology (gut motility, kidney and liver function). It explains why two people on the same dose have different response magnitudes.

Reading it again, the caveat matters more than the finding.

Taking post #24 at face value and following it one step further.

Bioavailability: oral semaglutide has low bioavailability (roughly 1%) due to peptide instability. That is why the oral dose (14 mg) is so much larger than the injectable dose. Comparing them by mass is meaningless.

That much is documented. The rest is how I have interpreted it.

Post #22 and I disagree about the size of the effect, not about the direction.

Fasting requirement for oral semaglutide: food and large fluid volumes reduce absorption. The fasting window (30 minutes before and 30 minutes after) is designed to maximise absorption. Violating it measurably reduces exposure.

The step people skip is the one I have spelled out.

Steady state is approached in roughly four to five half-lives. For a compound with a week-long half-life that is four to five weeks, which is where the escalation interval in the trials comes from.

Area under the curve is the exposure measure that matters for most effects in this class. Peak concentration matters more for tolerability.

Second-hand, so weight it accordingly.

Half-life determines how quickly concentration approaches steady state and does not determine what the steady-state concentration is. Dose and clearance determine that.

I checked the source rather than the summary, and they differ.

Post #26 describes the usual case. This is about the unusual one.

Between-person variability in exposure is substantial and is the reason two people on the same dose can have quite different plasma concentrations. That is inherent rather than a formulation defect.

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