Maintenance dosing: what is licensed, what is practised, and what is evidenced
What the labels permit, what clinicians do, and the size of the gap between them.
Titration
Escalation intervals, tolerability-led adjustment, plateau, and re-titration after an interruption.
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.
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…
The ceiling is a tolerability finding, not an efficacy one
We looked at what the dose-ranging data supports about going higher, and it is thinner and less flattering than the market assumes.
What the trials counted as intolerance
We set out the questions that distinguish a symptom to manage from a dose to change.
The restart nobody plans for
The convention — resume lower, re-escalate — is not caution. It follows directly from the elimination half-life.
The withdrawal trials, read as designs rather than warnings
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.
The eighteenth month, and the conversation that should have happened in the third
A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.
The shortage years, and what they taught about interruption
The trials studied planned withdrawal. Almost nobody stops that way.
What STEP 4 and SURMOUNT-4 actually established
A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.
What the anaesthetists said, and then said again
What endoscopic and ultrasound studies found about residual gastric content, and what the aspiration data does and does not support.
The mechanism behind the mechanism
The clinical effect profile is almost fully predictable from where the receptor is expressed, which is unusual and useful.
The eighteenth month, and the conversation that should have happened in the third
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.
The eighteenth month, and the conversation that should have happened in the third
Two withdrawal-design trials tell us what happens when treatment stops. Neither tells us what the lowest effective maintenance dose is.
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.
Escalating past the approved maximum, examined honestly
We looked at what the dose-ranging data supports about going higher, and it is thinner and less flattering than the market assumes.
Continued treatment against continued placebo: the comparison that settled it
The evidence on stopping is better than the evidence on almost anything else in this field, because somebody deliberately randomised it.
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 area postrema, and the anatomy of an unwanted effect
What scintigraphy and breath-test studies established about emptying rate, and what they did not.