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.
Maintenance
Page 6 of 9 of this archive, newest first.
Holidays, surgery, sickness: interruption in practice
Supply interruption is the commonest cause of unplanned re-titration in this market, and it is almost never framed that way.
Two-thirds back: the extension nobody expected to be the headline
A withdrawal trial answers a narrower question than it appears to. This piece states which question.
Three weeks off is a fresh start, whether or not you want one
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 lowest effective dose is a real concept with almost no data behind it
A survey of the maintenance evidence, which is shorter than the survey of the withdrawal evidence.
What the placebo arms of the withdrawal trials actually tell us
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.
Randomised withdrawal is the cleanest design in this field and the least discussed
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.
The upper rungs, ranked by evidence
Where the curve flattens, what flattens with it, and what does not.
What STEP 4 and SURMOUNT-4 actually established
A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.
Maximum tolerated is not maximum approved
Weight reduction in the long programmes flattens at roughly sixty to seventy-two weeks. The timing is consistent, predictable and almost never mentioned in advance.
The dose that got you here and the dose that keeps you here
The commonest real-world strategy in this drug class is the least studied one.
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.
Randomised withdrawal is the cleanest design in this field and the least discussed
The regain trajectories, arm by arm, with the estimands named.
The label says four weeks. The clinic says whatever holds.
The published ladder exists because a protocol needed a single number. Practice has never followed it exactly, and the regulatory file never assumed it would.
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.
What the placebo arms of the withdrawal trials actually tell us
What was withdrawn, from whom, after how long, and what was measured afterwards.
Why people actually stop, in the order they actually stop
Real-world persistence figures, with their definitions stated, because the definitions are doing most of the work.
Do you need the top of the ladder?
The dose-response curve in this class flattens near its top. That has direct consequences for whether the final rung is worth climbing.
The lead-in, the randomisation, and the year that followed
The regain trajectories, arm by arm, with the estimands named.
Weight regain is not a failure of willpower and it is not a mystery
Regain begins immediately, proceeds at a decelerating rate, and does not usually return to baseline within the observed follow-up. Each of those three clauses matters.