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.
Tirzepatide
Page 13 of 18 of this archive, newest first.
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 dose that got you here and the dose that keeps you here
What the labels permit, what clinicians do, and the size of the gap between them.
Why the bone question is harder than the muscle question
What the Journal would want measured before treating this as settled in either direction.
Accumulation, trough, and the exposure curve nobody draws for patients
An accumulation model, drawn from published parameters, with its assumptions stated.
Why people actually stop, in the order they actually stop
Real-world persistence figures, with their definitions stated, because the definitions are doing most of the work.
The advice is mostly reasonable. The certainty is not earned.
A tour of the source literatures, with an assessment of how far each legitimately reaches.
Stepping down against stopping: two decisions treated as one
These agents produce no dependence and no withdrawal syndrome. What a taper would be for is therefore a real question rather than an obvious one.
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.
Where the receptor is: a tissue-by-tissue account of tirzepatide’s reach
The same receptor population that produces the therapeutic effect produces the commonest adverse one.
From cell to clinic: where the extrapolation stops being safe
Receptor pharmacology is strong on average effects and almost silent on individual variation. That gap is where most reader questions live.
A guide to the results that will resolve themselves
Three different explanations for the same abnormal number, and how to tell them apart.
The lead-in, the randomisation, and the year that followed
The regain trajectories, arm by arm, with the estimands named.
Weight regain is not a failure of willpower and it is not a mystery
Regain begins immediately, proceeds at a decelerating rate, and does not usually return to baseline within the observed follow-up. Each of those three clauses matters.
The substudies, read properly: who was scanned, when, and with what
Both the reassuring reading and the alarming reading are supportable from the same tables. This piece sets out which is which.
Every fortnight, every third week, seasonally: an unstudied practice
An absence of evidence is not evidence of harm. It is also not a licence.
Stepping down against stopping: two decisions treated as one
The best argument for tapering is behavioural rather than pharmacological, and it deserves to be made on its own terms.
The lowest effective dose is a real concept with almost no data behind it
Dose reduction is not withdrawal, and the trials that tested withdrawal cannot be read as testing it.
Two scans, six weeks apart, and the arithmetic of believing the difference
A body-composition report gives four decimal places and no confidence interval. That is the whole difficulty in one sentence.
Holding a dose is a decision, not a failure
Reducing a dose is not going backwards. In a tolerability-limited class it is the mechanism by which the ceiling is found.