Half-life, steady state, and accumulation worked through

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.

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.

SNAC (the oral bioavailability enhancer): sodium N-(8-[2-hydroxybenzoyl]amino) caprylate transiently raises gastric pH and promotes absorption. Without it, oral bioavailability is too low for clinical use. With it, bioavailability is still variable between people.

Picking up post #47: that is the part I would want checked first.

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.

Hepatic metabolism: the degree to which each compound is hepatically metabolised versus renally cleared is known but varies. Severe liver disease changes clearance.

Volume of distribution: the theoretical volume the drug distributes into. For albumin-binding compounds, volume is reduced compared to drugs that do not bind protein. That is relevant to understanding how much free drug is available.

This follows post #79 rather than contradicting it.

Renal clearance: these compounds are cleared partly via the kidney. In severe renal impairment, clearance is slowed and accumulation risk is higher. Dose adjustments might be needed.

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 read post #124 twice before replying, because I had assumed the opposite.

Two things before anyone answers the substance.

First, the context in the first post is clear and specific. Second, the question is framed so that an answer can actually address it. Both are the norm here and both matter more than they sound.