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.
Maintenance
Page 2 of 9 of this archive, newest first.
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.
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.
Why people actually stop, in the order they actually stop
The trials studied planned withdrawal. Almost nobody stops that way.
Diminishing returns, quantified
The ceiling in this class is anatomical: the same receptor populations that suppress appetite provoke nausea, and they saturate together.
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 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.
Holding a dose is a decision, not a failure
A dose held long enough stops being a pause and becomes a maintenance decision. That transition is rarely made explicitly.
The trade has decided the ceiling is arbitrary. The trials disagree.
Where the curve flattens, what flattens with it, and what does not.
The supply gap as a clinical event
A supply interruption is a discontinuation with no notice, no taper and no plan. That is a distinct clinical situation.
The upper rungs, ranked by evidence
We looked at what the dose-ranging data supports about going higher, and it is thinner and less flattering than the market assumes.
The arithmetic of a step: what doubling a dose actually asks of you
We work the arithmetic out in full, because it is arithmetic and it is short.
Reading the semaglutide titration schedule as a regulatory artefact
The published ladder exists because a protocol needed a single number. Practice has never followed it exactly, and the regulatory file never assumed it would.
What a month without the drug does to tolerability
The convention — resume lower, re-escalate — is not caution. It follows directly from the elimination half-life.
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.
Do you need the top of the ladder?
The dose-response curve in this class flattens near its top. That has direct consequences for whether the final rung is worth climbing.
The dose that got you here and the dose that keeps you here
What the labels permit, what clinicians do, and the size of the gap between them.
Randomised withdrawal is the cleanest design in this field and the least discussed
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.