The interventions with trial support, and the much longer list without
Almost nothing in the standard management repertoire has been tested in a randomised trial in this specific population. We say what is extrapolated and from where.
Titration
Page 9 of 14 of this archive, newest first.
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.
Hydration, protein and the two failures that compound each other
Dietary measures are widely recommended, plausible on mechanism, and supported mainly by observational data and clinical experience.
Gallstones during rapid weight loss: drug, or weight loss?
We give background rates alongside trial rates, because an event occurring during treatment is not thereby caused by it.
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…
Antiemetics, laxatives and the thin literature underneath them
Constipation is the most tractable of the effects and the most consistently under-managed.
Every fortnight, every third week, seasonally: an unstudied practice
A great deal of practice has grown up around intermittent schedules. The randomised evidence for any of them is, as far as the Journal can establish, nil.
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.
Severity grading, and the gap between a grade and an experience
Almost every figure in circulation about tolerability comes from six publications. This is what they say.
The supply gap as a clinical event
The trials studied planned withdrawal. Almost nobody stops that way.
Reflux, early satiety, and the volume the stomach will accept
The clinical effect profile is almost fully predictable from where the receptor is expressed, which is unusual and useful.
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.
Dose-limiting: a definition worth being strict about
Roughly four to seven per cent of trial participants discontinued for adverse events, mostly gastrointestinal, mostly during escalation. That is the empirical size of the…
The lead-in, the randomisation, and the year that followed
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.
Delayed emptying explains some of this, and not all of it
What scintigraphy and breath-test studies established about emptying rate, and what they did not.
Tolerability is the ceiling, and the ceiling is personal
Roughly four to seven per cent of trial participants discontinued for adverse events, mostly gastrointestinal, mostly during escalation. That is the empirical size of the…
The interventions with trial support, and the much longer list without
We separate what is supported, what is reasonable, and what is folklore, and we do not pretend the boundaries are crisp.
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.
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.