Reflux, early satiety, and the volume the stomach will accept
The receptor populations that produce satiety and the ones that produce nausea overlap substantially. That is why the ceiling of this drug class is where it is, and it is…
Titration
Page 11 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 the placebo arms of the withdrawal trials actually tell us
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.
The area postrema, and the anatomy of an unwanted effect
A single drug producing both constipation and diarrhoea looks contradictory until the motility data is read properly.
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.
Residual stomach content on endoscopy: the studies
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.
Stepping down is part of titration
Nausea and gastric delay attenuate over weeks at an unchanged dose. That single physiological fact is the entire justification for holding.
The supply gap as a clinical event
Why the reason for stopping changes what happens afterwards.
Discontinuation rates, read honestly
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.
Do you need the top of the ladder?
A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.
What the tirzepatide 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 STEP 5 tells us about maintenance, and what it does not
Dose reduction is not withdrawal, and the trials that tested withdrawal cannot be read as testing it.
Dose-limiting: a definition worth being strict about
Roughly four to seven per cent of trial participants discontinued for adverse events, mostly gastrointestinal, mostly during escalation. That is the empirical size of the…
What actually helps, ranked by evidence
Almost nothing in the standard management repertoire has been tested in a randomised trial in this specific population. We say what is extrapolated and from where.
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.
Gallstones during rapid weight loss: drug, or weight loss?
Pancreatitis is rare, was adjudicated in the outcome programmes, and did not show the imbalance early case reports suggested.
Reading the dulaglutide 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.
Why people actually stop, in the order they actually stop
The trials studied planned withdrawal. Almost nobody stops that way.
Why your endoscopist wants to know about your injection
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.