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.
Maintenance
Dose reduction after target, intermittent schedules, and what evidence exists for either.
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.
The trade has decided the ceiling is arbitrary. The trials disagree.
Where the curve flattens, what flattens with it, and what does not.
The dose that got you here and the dose that keeps you here
Dose reduction is not withdrawal, and the trials that tested withdrawal cannot be read as testing it.
Do you need the top of the ladder?
Two withdrawal-design trials tell us what happens when treatment stops. Neither tells us what the lowest effective maintenance dose is.
Side effects, cost, supply, target: four reasons with four trajectories
Real-world persistence figures, with their definitions stated, because the definitions are doing most of the work.
The supply gap as a clinical event
Real-world persistence figures, with their definitions stated, because the definitions are doing most of the work.
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.
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.
The upper rungs, ranked by evidence
Where the curve flattens, what flattens with it, and what does not.
The supply gap as a clinical event
Why the reason for stopping changes what happens afterwards.
What STEP 4 and SURMOUNT-4 actually established
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 supply gap as a clinical event
Cost is the modal reason for discontinuation in every dataset we have seen, and it is absent from the clinical literature.
What the tirzepatide schedule assumes about a person it has never met
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
The dose that got you here and the dose that keeps you here
A survey of the maintenance evidence, which is shorter than the survey of the withdrawal evidence.
The upper rungs, ranked by evidence
Where the curve flattens, what flattens with it, and what does not.
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…
Randomised withdrawal is the cleanest design in this field and the least discussed
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.