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.
Maintenance
Page 8 of 9 of this archive, newest first.
Stepping down against stopping: two decisions treated as one
These agents produce no dependence and no withdrawal syndrome. What a taper would be for is therefore a real question rather than an obvious one.
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.
The lead-in, the randomisation, and the year that followed
The evidence on stopping is better than the evidence on almost anything else in this field, because somebody deliberately randomised it.
Maximum tolerated is not maximum approved
A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.
Side effects, cost, supply, target: four reasons with four trajectories
Why the reason for stopping changes what happens afterwards.
The eighteenth month, and the conversation that should have happened in the third
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.
Target dose, effective dose, and the distance between them
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.
Every fortnight, every third week, seasonally: an unstudied practice
What the exposure arithmetic says about a fortnightly schedule, and where the arithmetic stops being informative.
The supply gap as a clinical event
Cost is the modal reason for discontinuation in every dataset we have seen, and it is absent from the clinical literature.
What a month without the drug does to tolerability
The convention — resume lower, re-escalate — is not caution. It follows directly from the elimination half-life.
Diminishing returns, quantified
The ceiling in this class is anatomical: the same receptor populations that suppress appetite provoke nausea, and they saturate together.
What TRIUMPH-3 tells us about maintenance, and what it does not
A survey of the maintenance evidence, which is shorter than the survey of the withdrawal evidence.
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.
What happens when the drug is taken away: three randomised answers
The regain trajectories, arm by arm, with the estimands named.
The supply gap as a clinical event
Cost is the modal reason for discontinuation in every dataset we have seen, and it is absent from the clinical literature.
The label says four weeks. The clinic says whatever holds.
What the regulatory dossiers actually contain on dose selection is remarkably thin, and worth knowing before treating the ladder as settled science.
Escalating past the approved maximum, examined honestly
The ceiling in this class is anatomical: the same receptor populations that suppress appetite provoke nausea, and they saturate together.
Randomised withdrawal is the cleanest design in this field and the least discussed
The regain trajectories, arm by arm, with the estimands named.
The shortage years, and what they taught about interruption
A supply interruption is a discontinuation with no notice, no taper and no plan. That is a distinct clinical situation.