A supply gap is a pharmacological event
One omitted dose is a labelling question. Four omitted doses is a clinical one. The two are routinely conflated.
Titration
Page 14 of 14 of this archive, newest first.
What the trials counted as intolerance
We set out the questions that distinguish a symptom to manage from a dose to change.
What happens when the drug is taken away: three randomised answers
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.
What the cagrilintide schedule assumes about a person it has never met
The four-week step exists because four to five weeks is approximately how long a once-weekly drug takes to stop rising at a fixed dose. That is a good reason, and it is not…
The arithmetic of a step: what doubling a dose actually asks of you
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
What happens when the drug is taken away: three randomised answers
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.
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.
Target dose, effective dose, and the distance between them
Two withdrawal-design trials tell us what happens when treatment stops. Neither tells us what the lowest effective maintenance dose is.
Stepping down is part of titration
The practice is near-universal, clinically sensible, and supported by observational data rather than randomised comparison. We say which is which.
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.
The eighteenth month, and the conversation that should have happened in the third
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.
What STEP 4 and SURMOUNT-4 actually established
Two withdrawal-design trials tell us what happens when treatment stops. Neither tells us what the lowest effective maintenance dose is.
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.
Attribution is the hard part
We give background rates alongside trial rates, because an event occurring during treatment is not thereby caused by it.
Background rates, and why they matter for attribution
The features that should prompt urgent assessment, stated once and plainly.
The tolerability data everybody quotes and nobody reads
Almost every figure in circulation about tolerability comes from six publications. This is what they say.