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.
Titration
Page 3 of 14 of this archive, newest first.
Side effects, cost, supply, target: four reasons with four trajectories
The trials studied planned withdrawal. Almost nobody stops that way.
What the survodutide 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 the trial protocols permitted, and what the labels omitted
Nausea and gastric delay attenuate over weeks at an unchanged dose. That single physiological fact is the entire justification for holding.
What the trials adjudicated, and how
We give background rates alongside trial rates, because an event occurring during treatment is not thereby caused by it.
Holding a dose is a decision, not a failure
Every major phase 3 protocol in this class allowed escalation to be delayed for tolerability. Almost no product label explains the mechanics of doing so.
Reading the survodutide titration schedule as a regulatory artefact
What the regulatory dossiers actually contain on dose selection is remarkably thin, and worth knowing before treating the ladder as settled science.
Dose-limiting: a definition worth being strict about
An effect is dose-limiting when it prevents adequate intake, prevents normal activity, or produces a risk of its own. Discomfort alone is not the test.
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 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.
The lowest effective dose is a real concept with almost no data behind it
What the labels permit, what clinicians do, and the size of the gap between them.
When to stop escalating and when to stop entirely
We set out the questions that distinguish a symptom to manage from a dose to change.
Diminishing returns, quantified
The ceiling in this class is anatomical: the same receptor populations that suppress appetite provoke nausea, and they saturate together.
Hydration, protein and the two failures that compound each other
The intervention with the clearest evidence is the one nobody frames as an intervention: adjusting the dose.
Maintenance dosing: what is licensed, what is practised, and what is evidenced
Every withdrawal trial compared full dose against nothing. The clinically interesting comparison — full dose against a reduced one — has not been randomised.
Adverse events by dose, adverse events by week
Almost every figure in circulation about tolerability comes from six publications. This is what they say.
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.
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 happens when the drug is taken away: three randomised answers
What was withdrawn, from whom, after how long, and what was measured afterwards.
The ceiling is a tolerability finding, not an efficacy one
Where the curve flattens, what flattens with it, and what does not.