What the trials counted as intolerance
We set out the questions that distinguish a symptom to manage from a dose to change.
Nausea
The commonest reason for dose reduction and the commonest reason for discontinuation.
Background rates, and why they matter for attribution
Pancreatitis is rare, was adjudicated in the outcome programmes, and did not show the imbalance early case reports suggested.
Antiemetics, laxatives and the thin literature underneath them
We separate what is supported, what is reasonable, and what is folklore, and we do not pretend the boundaries are crisp.
Forty-four per cent: reading the nausea figure properly
Almost every figure in circulation about tolerability comes from six publications. This is what they say.
Adverse events by dose, adverse events by week
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.
The mechanism behind the mechanism
The clinical effect profile is almost fully predictable from where the receptor is expressed, which is unusual and useful.
Adverse events by dose, adverse events by week
Almost every figure in circulation about tolerability comes from six publications. This is what they say.
Dose-limiting: a definition worth being strict about
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.
What the trials counted as intolerance
The ceiling varies severalfold between people, and nothing measurable at baseline predicts where it sits.
Holding the dose before surgery: for whom, for how long
This is the single interaction with ordinary medical care that patients most need to disclose, and it is the one most often not asked about.
Antiemetics, laxatives and the thin literature underneath them
Dietary measures are widely recommended, plausible on mechanism, and supported mainly by observational data and clinical experience.
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.
Pancreatitis, obstruction, gallbladder: three things nausea can be
Rapid weight loss by any means raises gallstone risk. Separating that from a direct drug effect requires a comparator, and the trials have one.
Dose-limiting: a definition worth being strict about
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.
The incidence tables, read line by line
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.
Hydration, protein and the two failures that compound each other
The intervention with the clearest evidence is the one nobody frames as an intervention: adjusting the dose.
Adverse events by dose, adverse events by week
Almost every figure in circulation about tolerability comes from six publications. This is what they say.
What actually helps, ranked by evidence
We separate what is supported, what is reasonable, and what is folklore, and we do not pretend the boundaries are crisp.
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.
What the trials counted as intolerance
We set out the questions that distinguish a symptom to manage from a dose to change.