There is no discontinuation syndrome, and that changes the argument
The best argument for tapering is behavioural rather than pharmacological, and it deserves to be made on its own terms.
Titration
Page 6 of 14 of this archive, newest first.
What STEP 4 and SURMOUNT-4 actually established
The dose-response curve in this class flattens near its top. That has direct consequences for whether the final rung is worth climbing.
A supply gap is a pharmacological event
Concentrations fall by half a week, so a month away leaves a small fraction of steady state. Resuming at the previous dose presents the receptor with a step it has not seen…
The eighteenth month, and the conversation that should have happened in the third
What the trials measured was continuation against withdrawal. What patients want to know is continuation at a lower dose, and that study has largely not been done.
What happens when the drug is taken away: three randomised answers
The regain trajectories, arm by arm, with the estimands named.
Maintenance dosing: what is licensed, what is practised, and what is evidenced
A survey of the maintenance evidence, which is shorter than the survey of the withdrawal evidence.
The mechanism behind the mechanism
The clinical effect profile is almost fully predictable from where the receptor is expressed, which is unusual and useful.
A supply gap is a pharmacological event
One omitted dose is a labelling question. Four omitted doses is a clinical one. The two are routinely conflated.
The steps get smaller as the ladder gets higher, and that is deliberate
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
The dose that got you here and the dose that keeps you here
Every withdrawal trial compared full dose against nothing. The clinically interesting comparison — full dose against a reduced one — has not been randomised.
The mechanism behind the mechanism
The receptor populations that produce satiety and the ones that produce nausea overlap substantially. That is why the ceiling of this drug class is where it is, and it is…
Every fortnight, every third week, seasonally: an unstudied practice
An absence of evidence is not evidence of harm. It is also not a licence.
When to stop escalating and when to stop entirely
The ceiling varies severalfold between people, and nothing measurable at baseline predicts where it sits.
Maintenance dosing: what is licensed, what is practised, and what is evidenced
Dose reduction is not withdrawal, and the trials that tested withdrawal cannot be read as testing it.
The arithmetic of a step: what doubling a dose actually asks of you
The four-week step exists because four to five weeks is approximately how long a once-weekly drug takes to stop rising at a fixed dose. That is a good reason, and it is not…
Pancreatitis, obstruction, gallbladder: three things nausea can be
A small number of serious gastrointestinal events occur in people taking these drugs. Distinguishing them from the expected effect profile is the most consequential…
The restart nobody plans for
We work through the residual-exposure table so the decision can be made from numbers rather than from feel.
Escalating onto a rising curve
The four-week step exists because four to five weeks is approximately how long a once-weekly drug takes to stop rising at a fixed dose. That is a good reason, and it is not…
The shortage years, and what they taught about interruption
Cost is the modal reason for discontinuation in every dataset we have seen, and it is absent from the clinical literature.
Gallstones during rapid weight loss: drug, or weight loss?
The features that should prompt urgent assessment, stated once and plainly.