When to stop escalating and when to stop entirely
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.
Delayed gastric emptying
Page 4 of 6 of this archive, newest first.
What the trials counted as intolerance
We set out the questions that distinguish a symptom to manage from a dose to change.
When to stop escalating and when to stop entirely
We set out the questions that distinguish a symptom to manage from a dose to change.
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.
Antiemetics, laxatives and the thin literature underneath them
Constipation is the most tractable of the effects and the most consistently under-managed.
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.
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…
Why your endoscopist wants to know about your injection
Holding a dose before a procedure has a kinetic problem: a weekly drug with a seven-day half-life cannot be cleared by skipping one injection.
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…
Hydration, protein and the two failures that compound each other
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.
Holding the dose before surgery: for whom, for how long
The evidence is real, modest, and mostly retrospective. The guidance is correspondingly cautious and has been revised toward individualisation.
The tolerability data everybody quotes and nobody reads
Trial adverse-event tables count episodes reported to a study nurse. They are the best data we have and they systematically under-record the mundane.
Gallstones during rapid weight loss: drug, or weight loss?
Pancreatitis is rare, was adjudicated in the outcome programmes, and did not show the imbalance early case reports suggested.
What actually helps, ranked by evidence
The intervention with the clearest evidence is the one nobody frames as an intervention: adjusting the dose.
The effect profile, predicted from an expression map
Delayed gastric emptying is a mechanism that becomes an adverse effect above a threshold. It is not a complication in the ordinary sense.
Reflux, early satiety, and the volume the stomach will accept
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…
Delayed emptying explains some of this, and not all of it
The clinical effect profile is almost fully predictable from where the receptor is expressed, which is unusual and useful.
The area postrema, and the anatomy of an unwanted effect
A single drug producing both constipation and diarrhoea looks contradictory until the motility data is read properly.