The label says four weeks. The clinic says whatever holds.
Deviation from the printed ladder is not non-compliance. In this class it is the modal behaviour of competent prescribing.
Titration
Page 7 of 14 of this archive, newest first.
The interventions with trial support, and the much longer list without
The intervention with the clearest evidence is the one nobody frames as an intervention: adjusting the dose.
Diminishing returns, quantified
Where the curve flattens, what flattens with it, and what does not.
Delayed emptying explains some of this, and not all of it
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…
The mechanism behind the mechanism
Delayed gastric emptying is a mechanism that becomes an adverse effect above a threshold. It is not a complication in the ordinary sense.
The effect profile, predicted from an expression map
A single drug producing both constipation and diarrhoea looks contradictory until the motility data is read properly.
Do you need the top of the ladder?
A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.
What the trial protocols permitted, and what the labels omitted
The practice is near-universal, clinically sensible, and supported by observational data rather than randomised comparison. We say which is which.
Escalating onto a rising curve
We work the arithmetic out in full, because it is arithmetic and it is short.
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 upper rungs, ranked by evidence
Where the curve flattens, what flattens with it, and what does not.
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…
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.
Gallstones during rapid weight loss: drug, or weight loss?
The features that should prompt urgent assessment, stated once and plainly.
What a month without the drug does to tolerability
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…
What STEP 8 tells us about maintenance, and what it does not
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
A single drug producing both constipation and diarrhoea looks contradictory until the motility data is read properly.
Delayed emptying explains some of this, and not all of it
A single drug producing both constipation and diarrhoea looks contradictory until the motility data is read properly.
Maintenance dosing: what is licensed, what is practised, and what is evidenced
Every withdrawal trial compared full dose against nothing. The clinically interesting comparison — full dose against a reduced one — has not been randomised.
Tolerability is the ceiling, and the ceiling is personal
An effect is dose-limiting when it prevents adequate intake, prevents normal activity, or produces a risk of its own. Discomfort alone is not the test.