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.
Semaglutide
Page 8 of 18 of this archive, newest first.
Percentage of loss, absolute kilograms, and the sleight of hand between them
The trials measured mass. Nobody measured whether the participants got weaker.
The out-of-range flag is a statistical convention with a printer attached
A twelve-analyte panel in a perfectly healthy person has roughly even odds of producing at least one flagged result.
Escalating onto a rising curve
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
Percentage of loss, absolute kilograms, and the sleight of hand between them
What was pre-specified, what was exploratory, and what was calculated afterwards by people who did not run the trial.
Every fortnight, every third week, seasonally: an unstudied practice
An absence of evidence is not evidence of harm. It is also not a licence.
Maintenance dosing: what is licensed, what is practised, and what is evidenced
Dose reduction is not withdrawal, and the trials that tested withdrawal cannot be read as testing it.
Which results should be repeated before they are investigated
What the pivotal programmes measured and how often, which is a more defensible template than most published monitoring schedules.
A reference interval is not a target, and a result outside one is not a diagnosis
Almost every misreading of a laboratory panel is a misunderstanding of what a reference interval is and how much a result has to move before the movement means anything.
Gastric emptying is a mechanism, not a side effect
The central effects are not a bonus. On the current evidence they are the principal mechanism of weight loss.
The eighteenth month, and the conversation that should have happened in the third
The dose-response curve in this class flattens near its top. That has direct consequences for whether the final rung is worth climbing.
SURMOUNT-2 was built to answer the stopping question, and it did
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.
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.
The restart nobody plans for
We work through the residual-exposure table so the decision can be made from numbers rather than from feel.
What the protein literature actually shows, and in whom it was shown
Where the familiar figures come from, what populations they were measured in, and how far the extrapolation reaches.
A year after stopping: what the trials found at the far end
Fat mass, lean mass, and the composition of regained weight — the thinnest literature in this piece.
The shortage years, and what they taught about interruption
Real-world persistence figures, with their definitions stated, because the definitions are doing most of the work.
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.
Two-thirds back: the extension nobody expected to be the headline
The evidence on stopping is better than the evidence on almost anything else in this field, because somebody deliberately randomised it.