Target dose, effective dose, and the distance between them
The dose-response curve in this class flattens near its top. That has direct consequences for whether the final rung is worth climbing.
Maintenance
Page 7 of 9 of this archive, newest first.
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.
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.
Maintenance dosing: what is licensed, what is practised, and what is evidenced
A survey of the maintenance evidence, which is shorter than the survey of the withdrawal evidence.
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.
A schedule that bends does not break
Nausea and gastric delay attenuate over weeks at an unchanged dose. That single physiological fact is the entire justification for holding.
What the placebo arms of the withdrawal trials actually tell us
The evidence on stopping is better than the evidence on almost anything else in this field, because somebody deliberately randomised it.
Diminishing returns, quantified
Where the curve flattens, what flattens with it, and what does not.
Target dose, effective dose, and the distance between them
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.
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.
A year after stopping: what the trials found at the far end
The physiology of regain was described a decade before these drugs, and it explains the trajectory without invoking anything specific to them.
What the tirzepatide schedule assumes about a person it has never met
We work the arithmetic out in full, because it is arithmetic and it is short.
What STEP 5 tells us about maintenance, and what it does not
Dose reduction is not withdrawal, and the trials that tested withdrawal cannot be read as testing it.
The lowest effective dose is a real concept with almost no data behind it
The commonest real-world strategy in this drug class is the least studied one.
Randomised withdrawal is the cleanest design in this field and the least discussed
The regain trajectories, arm by arm, with the estimands named.
Why people actually stop, in the order they actually stop
A supply interruption is a discontinuation with no notice, no taper and no plan. That is a distinct clinical situation.
Escalating onto a rising curve
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
A schedule that bends does not break
Nausea and gastric delay attenuate over weeks at an unchanged dose. That single physiological fact is the entire justification for holding.
What STEP 4 and SURMOUNT-4 actually established
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.
Three weeks off is a fresh start, whether or not you want one
Supply interruption is the commonest cause of unplanned re-titration in this market, and it is almost never framed that way.