Two-thirds back: the extension nobody expected to be the headline
The regain trajectories, arm by arm, with the estimands named.
Titration
Page 12 of 14 of this archive, newest first.
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.
The shortage years, and what they taught about interruption
Cost is the modal reason for discontinuation in every dataset we have seen, and it is absent from the clinical literature.
Pancreatitis, obstruction, gallbladder: three things nausea can be
Pancreatitis is rare, was adjudicated in the outcome programmes, and did not show the imbalance early case reports suggested.
On-off cycling, and the argument from receptor biology that does not hold
The schedules in circulation, described accurately, with their evidentiary status attached.
Background rates, and why they matter for attribution
We give background rates alongside trial rates, because an event occurring during treatment is not thereby caused by it.
A schedule that bends does not break
Reducing a dose is not going backwards. In a tolerability-limited class it is the mechanism by which the ceiling is found.
The lead-in, the randomisation, and the year that followed
The evidence on stopping is better than the evidence on almost anything else in this field, because somebody deliberately randomised it.
Escalating past the approved maximum, examined honestly
Where the curve flattens, what flattens with it, and what does not.
What the cagrilintide schedule assumes about a person it has never met
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
Holding the dose before surgery: for whom, for how long
This is the single interaction with ordinary medical care that patients most need to disclose, and it is the one most often not asked about.
Background rates, and why they matter for attribution
A small number of serious gastrointestinal events occur in people taking these drugs. Distinguishing them from the expected effect profile is the most consequential…
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.
The incidence tables, read line by line
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.
What the trials counted as intolerance
We set out the questions that distinguish a symptom to manage from a dose to change.
Forty-four per cent: reading the nausea figure properly
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.
Why people actually stop, in the order they actually stop
Cost is the modal reason for discontinuation in every dataset we have seen, and it is absent from the clinical literature.
SURPASS-3 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.
Reflux, early satiety, and the volume the stomach will accept
A single drug producing both constipation and diarrhoea looks contradictory until the motility data is read properly.